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Endoscopic Submucosal Dissection For Early Colorectal Cancer And Precancerous Lesions And Confocal Laser Endomicroscopy Value In The Follow-up

Posted on:2014-04-13Degree:MasterType:Thesis
Country:ChinaCandidate:L ShaoFull Text:PDF
GTID:2254330425950169Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Background and Objection:Colorectal cancer is one of the most common malignancy in the world, the mortality rate of malignancies is second。In the United States,Colorectal cancer is the third most common malignancy, in2011,141,210new cases were diagnosed with colorectal cancer,49,380deaths, accounting for about9%of all cancer-related deaths; in the country, colorectal cancer is the fourth most common malignancy, approximately150,000patients were newly diagnosed every year,25%has occurred metastasis when diagnosed. The early is mostly asymptomatic, symptoms and transfer is mostly in the late. Colorectal cancer prognosis has a positive correlation between the size of the lesions and staging,5-year survival rate of early colorectal cancer patients without regional lymph node and distant metastasis is greater than90%, while late less than10%. Despite surgery and chemotherapy innovation, the survival rate of patients with advanced colorectal cancer is still poor. Since still a lack of a better way to prevent colorectal cancer, so the most effective measures to improve the prognosis and the survival rate of colorectal cancer is treatment of early colorectal cancer and precancerous lesions.In recent years, with the continuous progress of endoscopic techniques, new diagnostic endoscopic continues to emerge, such as chromoendoscopy, high-resolution digital staining endoscopy, endoscopic ultrasound, confocal laser endomicroscopy,et al,to be the technical basis for early detection and diagnosis of early colorectal cancer. Chromoendoscopy sprays the pigment on the surface of the lesion to make a sharp contrast between the diseased mucosa and normal mucosa and to targeted biopsy, plus colorectal pit pattern of enlarge colorectal endoscopic to improve the detection rate of early colorectal cancer. In recent years, the electronic staining endoscopy,such as NBI, FICE and I-Scan,has also been rapid progress. FICE (Fuji intelligent chromo endoscopy, FICE) technology is artificial intelligent electronic dyeing technology, use spectroscopic principle, improve the detection of superficial lesions through selective processing maximum light information on the clinical significance, while increasing the contrast between the lesion and the surrounding tissue structure, tiny blood vessels and surrounding tissue. NBI (narrow-band imaging, NBI) technology is narrow band imaging technology, mainly used for observation of the micro-duct morphology and micro vessels on the surface of gastrointestinal mucosal, to find some lesions that difficult to be found by the ordinary, and to improve the diagnostic accuracy. I-scan technology is high-resolution digital chromoendoscopy. That is Pentax’s new inventive endoscopic techniques in recent years.there are two main features:First, high-resolution (HDTV), CCD in the end of the endoscopy is1.3million pixels that make lesions easier to identify; Second, the three modules of the digital staining (also known as electronic staining, i.e. i-scan), including surface-enhanced (CE), contrast enhancement (SE), tone enhancement (TE), the vascular V mode, duct P mode. According to the different positions of the digestive tract, it is divided into modes, such as the esophagus TE-e, stomach TE-g, the colorect TE-c, and nature of the lesions can be distinguished by the combination of all three. Pentax endoscopy system has two main characteristics:HDTV+i-scan, respectively, corresponding to traditional endoscopic magnification and staining function, has the same diagnostic value of the traditional enlarge staining endoscopy to some extent, so that make the lesions more clear, significantly increase detection rate of small precancerous lesions and early colorectal cancer. Endoscopic ultrasonograpy(Endoscopic ultrasonograpy, EUS) can judge the origin of the lesion, depth of invasion, blood supply and peripheral lymph node metastasis by the judgment of the nature of the lesion and surrounding tissue echo. Confocal laser endomicroscopy (confocal laser endomicroscopy CLE) is a combination of confocal laser microscopy and electronic endoscopy,can directly access to the in vivo mucosal and submucosal histological image, known as "optical biopsy", and can guide targeted biopsies and improve the accuracy of the histopathological examination. As the the above endoscopic technology continues to mature, the diagnoses of tiny mucosal lesions reached a high level, with understanding of the treatment effect of early colorectal cancer and improving ideas of screening, such as opportunistic screening, high-risk groups screening, especially step-by-step implementation of natural population screening, there have been the trend of detection and diagnosis of a growing number early colorectal cancer. In Asia39%of colorectal cancer is early diagnosis. Professor Zheng Shu in China have done a lot of work in this area, Zhejiang Haining early screening and treatment of local colorectal cancer mortality in the15years dropped by40%.20,353cases by colonoscopy during the same period,1,087cases of colorectal cancer (5.3%colonoscopy detection rate). Cases of early cancer were146, accounting for13.4%, higher than the surgical detection rate in the same period. The radical premise of Early colorectal cancer should ensure the quality of life of the patients, despite the implementation of laparotomy or laparoscopic radical surgery is one of the effective treatment of early colorectal cancer, but because of surgical laparotomy trauma and risky, especially complications such as severe infection, adhesions, obstruction, anastomotic stenosis seriously affect the quality of life, so the trend in treatment of early colorectal cancer is minimally invasive, which including a lot of exploration and clinical research of minimally invasive endoscopic treatment. Since the1960s, first reported by Niwa H that endoscopic resection used for polypectomy by high-frequency power, people have endoscopic minimally invasive treatment philosophy. In recent years, with the development of the treatment of endoscopic and the invention and application of various assistive devices, endoscopic mucosal resection (Endoscopic Mucosal Resection, EMR) and endoscopic mucosal dissection (Endoscopic Submucosal Dissedtion, ESD) has become a standard minimally invasive treatment for digestive early cancer. Endoscopic mucosal resection (EMR) was first developed from submucosal injection of saline to remove colon sessile polyp reported by Dyhle in1973. Multi-Tian Zhenghong first used this technology for diagnosis and treatment of early gastric cancer in1984, and named exfoliative biopsy (Strip biopsy), also known as "endoscopic mucosal resection (EMR). Since then, with the improvement and invention of endoscopic techniques and equipment, EMR technology continuous improvement and innovation:the transparent cap (EMR with A Cap, EMRC), ligation method (EMR with Ligation, EMRL), submucosal injection, mucosal fragments resection,et al. Limitations and integrity of larger lesions and early cancer residual by EMR may encourage people to think about the newer technologies to peel larger, more complete organization. In1994Takekoshi invented a new electric knife (Insulated-tip Knife, IT knife) with ceramic insulation head on tip, allowing one-time complete resection on the greater gastrointestinal mucosa lesions. In1999Japanese experts Gotoda T first reported the use of IT knife for lesions complete resection, that is endoscopic mucosal dissection (ESD), then new equipment continued to the ranks of the ESD treatment. ESD is initially used for early gastric cancer, and is en bloc resection for large superficial tumors, with less trauma, treatment of low cost, high cure rate of successful en bloc complete resection of the lesion, low recurrence rate, the similar surgical effect, and without the surgical risk and postoperative serious impact on quality of life of the most of the patients. ESD has safe and exact effect in the treatment of stomach, early esophageal cancer and precancerous lesions, in recent years, the indications of ESD has expanding,applied to rectal cancer treatment has been reported and confirmed its security, but compared with the stomach, small intestine, tortuous, thin wall, and the presence of intestinal flora, thus technical difficulty, long operation time, prone to bleeding and perforation after submucosal resection, so there are few reports about the treatment effect and safety of ESD for early colorectal cancer and precancerous lesions, especially for early transverse colon and sigmoid colon cancer.How to early find disease recurrence in the ESD postoperative follow-up is clinical problems. ESD postoperative follow-up for early colorectal cancer requires review colonoscopy and local biopsy to determine residual and recurrence. But biopsy, but the biopsy samples only represent parts of the case, do not represent the entire lesion, and can not conduct real-time observation and targeted biopsy in body tissue. In recent years, confocal laser endomicroscopy as "optical biopsy" technology can predict colorectal pathology in the body, real time histological changes and to guide targeted biopsy in the diagnosis of colorectal cancer, but using confocal laser endomicroscopy in follow-up to monitor postoperative recurrence of ESD has not been reported. In this study, patients with endoscopic highly suspicious or clear for early colorectal cancer underwent ESD treatment, the pathological screening a total of12lesions including8patients with early colorectal cancer and4patients with high-grade intraepithelial neoplasia (CIN), observation and follow-up to explore the efficacy and safety of ESD treatment and the value of confocal laser endomicroscopy in the follow-up.Subjects and Methods1subjectsPatients underwent ESD treatment for highly suspicious or clear for early colorectal cancer after endoscopy on Digestive Endoscopy Center of the Third Affiliated Hospital of Southern Medical University from November2009to December2012. A total of12patients were enrolled in the study after operative pathological screening,8cases with early colorectalcancer (including2cases of expand ESD after endoscopic mucosal resection (EMR) with pathological diagnosis of early cancer) and4cases with high-grade intraepithelial neoplasia.8males and4females, mean age is52.5±11.1years old.1case located in the transverse colon,1case in sigmoid colon,2cases in the junction of the rectum and sigmoid colon,8cases in the rectum. The size of the lesion is1.5±0.6cm. All patients and their families signed informed consent. Inclusion criteria:preoperative high suspicious or clear for early colorectal cancer, lesions in the mucosa or submucosa without lymph node metastasis after endoscopic ultrasound, regardless size of the lesion. Exclusion criteria:endoscopic surgical contraindications, revealed lesions infiltration to the muscularis propria affter endoscopic ultrasound examination, refuse to endoscopic surgery.2methods Perffect preoperative examination after hospitalization, use endoscopic ultrasound to determine the depth and range of submucosal lesions,combing gland orifice and biopsy result to screening and guide ESD treatment. I-scan electron staining gland port of all patients is ⅢL-Ⅳ type or the type in the above. Do ESD preoperative biopsy.Professional anesthesiologists give patients intraoperative intravenous anesthesia with sufentanil and import propofol injection, and give oxygen and ECG monitoring for vital signs. There are currently no domestic various correlation length knives and coagulation forceps and transparent cap at the end of the colorectal for colonoscopic ESD, so this study use to complete this endoscopic surgery. Using gastroscopy to complete is more flexible and convenient than colonoscopy, coupled with the experience of a large number of upper gastrointestinal ESD by gastroscopy, it has higher success rate.ESD includes the following five steps:(1) Tags:use argon plasma coagulation (APC) to coagulate (output power35w) at the edge of the lesion0.5-1.0cm, interval of2-3mm;(2) submucosal injection:a mixed solution of1ml epinephrine and100ml of normal saline, add a small amount of indigo carmine,multi-point submucosal injection at the edge of the lesion outside of the marked, about2-3ml one point, repeated injections until the lesions was significantly lift;(3) lesions circumcision: use Hook knife or Daulknife to cut the lateral mucous along the margin markers of the lesion lesion (Enddo-cut mode,50W output power);(4) peeling lesions:With the transparent cap, repeated submucosal injection in order to maintain the full lifting of the lesion, use hook electric knife or IT2knife to strip lesions from the submucosa (Enddo-cut mode,50W output power) depending on the circumstances, until the complete stripping of the diseased tissue. If bleeding in stripping process, use knife to directly coagulate bleeding points, or Coagugrasper to clip bleeding points to coagulation;(5) wound treatment:using argon or coagulation forceps for wounds visible small blood vessels after removal of the lesion to avoid delayed bleeding. Using strong APC to shotcrete entire wound to avoid residual possible lesions, the depth is up to3-5mm.Titanium sutures some or all of the operative wound. ESD postoperative conventional ECG monitoring of vital signs6-8hours,fasting, conventional infusion, the use of drugs to stop bleeding, observation of the presence or absence of blood in the stool, abdominal symptoms and signs.liquid diet after2-3days without clinical manifestations and check abnormal. Recording indicators,such as postoperative vital signs, abdominal pain, bloody diarrhea, postoperative pathology results,bleeding,perforation,etc.Colonoscopy follow-up whenl,3,6months and1year after operation, with confocal laser endomicroscopy to observe wound healing and tumor recurrence and guidance of targeted biopsy. With2%sodium fluorescein1ml of skin test before confocal endoscopy, there is no allergic reaction before confocal endoscopy. After founding lesion, the intravenous injection of10%sodium fluorescein10ml, within30S the intestinal mucosa yellow color is visible, that time is to confocal laser endomicroscopy examination. In checking, the end of the endoscopy is placed on lesion surface and in close contact, two regulation button on the handle control the confocal scanning plane depth. Multi-site confocal laser endomicroscopy scan is for four-phase limit of the lesion mucosa and perilesional mucosa near3cm to lesion mucosa, take biopsy for4points. To analyse ESD technology efficacy and safety of resection of early colorectal cancer through the analysis of the clinical data of these patients and post-operative follow-up, tumor diameter, operating time, en bloc resection rate, histological curative resection rate, recurrence rate, complications and comparing confocal laser microendoscopy with pathology.Using SPSS13.0statistical software to analyze, the mean of measurement data using x±s,count data using x2test,ESD postoperative histopathology as the good standard,use Kappa coefficient and McNemar test to compare en bloc pathology after ESD and preoperative endoscopic biopsy, P≤0.05for the difference was statistically significant.ResultA total of12patients signing consent were included in the study from November2009to December2012, including8males and4females, the male to female ratio is2:1. The youngest is26years old, the oldest66years, average age is52.5±11.1years old. The tumor size is1.0-3.0cm, and the average size is1.5±0.6cm.9cases<2.0cm,3cases≥2.0cm. The morphology of the tumor type has10elevated type (type Ⅰ),2superficial elevated type (Ⅱa), including1elevated type has cancer tissue residues at the cutting edge after postoperative pathology. Mucosal pit of all tumors are ⅢL-Ⅳ type or more. EUS accuracy rate is91.7%(11/12), including one patient with preoperative ultrasound showed no myometrial invasion, without complete intraoperative submucosal injection uplift, considered myometrial invasion, and laparotomy confirmed it after communication with patients and the family.ESD operation is in40-110minutes, the average operating time was71.7±23.3minutes. En bloc resection rate was91.7%(11/12),1patient with lifting sign negative after submucosal injection, may infiltration, then turn surgical laparotomy and pathologically confirmed adenocarcinoma infiltrating the intrinsic muscles layer. Histological curative resection rate was83.3%(10/12), including2cases of incomplete resection:1adenocarcinoma after postoperative pathological examination, with cancer tissue residues at cutting edge, no recurrence when follow-up, the patient refused additional surgical laparotomy, continue to follow-up; another1patient with negative lifting sign off intraoperative submucosal injection, then turn the surgical laparotomy. Pathology confirmed adenocarcinoma infiltrating the muscularis propria. Preoperative biopsy diagnosis of endoscopic highly suspected early cancer lesions was50%(6/12). Preoperative biopsy in the diagnosis of early colorectal cancer was2lesions, precancerous lesions was10patients (10 lesions), after massive histopathology confirmed four cases were high-grade intraepithelial neoplasia (CIN), three cases were mucosal cancer,5cases adenocarcinoma (3cases of submucosal shallow cancer cutting edge no residue,1case of submucosa cancer cutting edge with residue,1case of adenocarcinoma infiltrating the muscularis layer, laparotomy confirmed).En bioc histopathological diagnosis rate after ESD or EMR wass91.7%(11/12).10patients were diagnosed with adenoma and high-grade intraepithelial neoplasia (CIN) by preoperative biopsy, preoperative pathology confirmed two cases were adenoma local cancer (both confirmed by large biopsy of EMR, additional ESD expanding mucosal resection),4cases of submucosal adenocarcinoma (3cases of superficial cancer of the submucosa cutting edge no residue,1case of the submucosa adenocarcinoma cutting edge with residue),4cases of high-grade intraepithelial neoplasia (CIN). Another two cases of preoperative biopsy diagnosis were early colorectal cancer, postoperative pathology confirmed1case of adenocarcinoma infiltrating the muscularis layer and another case of mucosa cancer.ESD intraoperation has a small amount of bleeding, successful hemostasis by coagulation forceps and APC (argon plasma coagulation,APC).1case was postoperative delayed bleeding, accounting for8%(1/12), stopped after conservative treatment.16.7%(2/12) of patients had postoperative abdominal pain, mild abdominal pain. All cases had no perforation.1case transfering Laparotomy did not undergo endoscopic follow-up,1cases of submucosa cancer resection margin with residue refused to add surgical surgery,and lost to follow-up.The remaining10cases were successful follow-up.Colonoscopy follow-up is the wound healing after1-3months.The average follow-up time is17.4±9.1months,10patients of the successful follow-up without lesions residual and recurrence,including3cases of superficial cancer of the submucosa cutting edge no residue after ESD.6patients using confocal laser microendoscopy to follow-up and guide targeted biopsy showed no tumor residual and recurrence.Conclusion1. This study suggests it must early do ESD to patients with highly questionable early cancer and precancerous lesions to achieve en bloc resection of the lesion and, and can improve early cancer detection rate by comparing en bioc biopsy with endoscopic biopsy.2. Endoscopic ultrasonograpy evaluation to the depth of invasion of colorectal early cancer has some guidance value.3. Thin colon wall, many folds of the intestine, great variation of the intestine toward, so the colon ESD operation is difficult, especially the transverse colon, sigmoid and the junction of the rectal and the sigmoid,need special attention in order to avoid complications such as bleeding and perforation.4. ESD has a higher en bloc resection rate and histological curative resection rate, is a safe and effective method for a diagnosis and treatment of early colorectal cancer and precancerous lesions. Confocal laser endomicroscopy likely has an important role in the postoperative follow-up of early colorectal cancer, first report, the small number of cases, needs further study.
Keywords/Search Tags:Endoscopic submucosal dissection, early colorectal cancer, precancerous lesions, confocal laser endomicroscopy
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