A Study On Diagnosis And Treatment Of The Digestive Endoscopy, Galectin-3and P27to Early Gastric Cancers And Precancerous Lesion

Objective: Gastric carcinoma is one of the most common malignant tumors, and isthe second commonest cause of cancer deaths worldwide. About87000new gastriccancer cases are diagnosed every year on a global scale. There is a considerablegeographical variation in the incidence of this cancer. It is reported that incidence ratesare high in eastern Asia, and low in Europe, North America and Africa. Chinese havehigh gastric cancer rates, which are only less than those found in Korea and Japan. Theprognosis of gastric carcinoma is closely related to the stage of disease at the time ofdiagnosis. The survival rate is greater than90%in5years for early gastric cancer, butthe prognosis is very poor for advanced gastric cancer. Therefore, early diagnosis ofgastric cancer is very important for an excellent prognosis. However, since mostpatients with early gastric carcinoma do not have specific symptoms, it is difficult todistinguish early gastric carcinoma from benign peptic ulcer or gastritis, and only about10-20%of gastric cancers are diagnosed as early cancers in many countries, and onlyabout4-10%of patients with gastric cancer are diagnosed as early cancer in China asper the statistics, which is even lower. Moreover, most of those patients with gastriccancer who are diagnosed as early cancer in China have been treated with surgicalresection of subtotal gastrectomy and lymph node dissection same as for the advancedgastric cancer. It is a top urgent task to increase the rate of diagnosis of early gastriccancer in China and to select the rational therapy with minimum trauma but equivalenteffects of surgical operation so as to improve the prognosis and life quality of thepatients of gastric cancer.Endoscopy in combination with pathological diagnosis is still regarded as the goldstandard. But the expressions of many precancerous lesions and early gastric cancer are so subtle that they can be hardly distinguished from benign lesions. With thedevelopment of endoscopic imaging technology, some endoscopic imaging modalities,such as magnifying narrow-band imaging (NBI) endoscopy, have been used recently forthe diagnosis of early gastric cancer. Although many studies have reported that thisendoscopic imaging modality can increase the rate of diagnosis of early cancers andprecancerous lesions by enhancing visualization, there are few studies about comparisonbetween NBI and conventional endoscopy.The development of molecular biological technologies provides a powerful basisfor the early diagnosis of gastric cancer. Some tumor markers have apparent changes inprecancerous lesions and early gastric cancer, so precancerous lesions and early gastriccancer can be found earlier with the detection of those markers combined withendoscopy, and this can provide evidence for screening high risk groups and clinicalcomprehensive diagnosis. In our previous studies, Galectin-3protein expressiondetected by immunohistochemistry was on the increase from the normal gastric mucosato advanced gastric cancer, while P27protein expression was on the decrease. So theexpressions of those two proteins were just opposite. Whether this result can be provenby other test methods will provide more bases for the search of the molecular biologicalindexes for the diagnosis of early gastric cancer.The key to gastric cancer treatment is the thorough resection of the focus and thelymph gland that tends to metastasis. In the past, the treatment of early gastric cancerwas same as that of the advanced gastric cancer in that the surgical radical resection andlymph node dissection were adopted, local excision of gastric lesion and segmentalresection, or partial resection preserving pylorus and vagus nerve function was used,while part of stomach must be excised in all cases with higher rate of complications andmortality. If deeper invasion or positive surgical margin is found by the post-operationpathological diagnosis, another operation must be carried out. So the life quality of thepatients after the operation is similar to that of the patients with advanced gastric cancer.The treatment of early gastric cancer should try to reduce the trauma as much aspossible while achieving the effects to improve the life quality of the patients. In recentyears, thanks to the progress of the endoscopic technology and the development of thetherapeutic devices, the use of EMR or ESD endoscopic technology for treatment hasbegun, which maintains the integrity of the digestive tract with significant improvementof life quality. Also, the complete tissue pathological sample can be obtained withoutsurgical operation, facilitating the selection of correct subsequent clinical therapy and avoiding unnecessary gastrectomy. Although this therapy has the advantages that areunmatched by the surgical operation, there are few clinical studies on the comparisonbetween the EGC endoscopic mucosal resection and the surgical laparotomy treatment.The objective of this study is to explore the magnifying narrow-band imagingendoscopic changes and the changes of the molecular biological indexes in theprecancerous lesion and early gastric cancer stage, to reveal their values in the diagnosisof precancerous lesion and early gastric cancer, to compare and analyze the treatment ofearly gastric cancer with endoscopic mucosal resection and the surgical laparotomy invarious aspects, and to provide the theoretical basis for the search of the reliablediagnosis and treatment methods of precancerous lesion and early gastric cancer.This thesis can be divided into three sections:First, the diagnosis of early gastric cancers and precancerous lesion by using theendoscope inspection of enlarging narrow band imaging (hereinafter to be referred asNBI);Second, the meanings of Galectin-3and P27expressions in the development ofgastric cancer;Third, a multi-angle comparative study between the mucosectomie endoscopiqueand early gastric cancer treatment in surgical operation.Methods:1、526patients were suspected to be early gastric cancers orprecancerous lesion in conventional endoscope inspection, including122who wereconfirmed as early gastric cancers or precancerous lesion evidenced by a tissuespecimen pathologically in endoscopic biopsy and endoscopic or surgical resection,among whom the youngest one was16years old and the oldest was94years old (83males and39females) with their average age at63.5±14.1years old. All122patientsaccepted inspections and diagnosis including the conventional endoscope, enlarged NBIand the magnifying chromoendoscopy. The imaging qualities were commented duringthe inspection process and the morphology features, gastric concave classifications andblood capillaries in different kinds of forms of endoscopy were also analyzed. If there isany stomach malignant epithelial neoplasm and high grade intraepithelial neoplasiaoccurred in the tissue slices, then it is to be considered as positive which can be used tocomment the correctness of endoscopic diagnosis.2、By using immunohistochemistry (S-P) and RT-PCR methods, the expressions ofGalectin-3, P27proteins and mRNA were inspected among40cases of normal gastricmucosa,50cases of atypical hyperplasia,56cases of early gastric cancers and46cases of advanced gastric carcinoma. The selected standards for each group are as follows:(1)Cases of normal gastric mucosa group: no stomach neoplasms history, smoothendoscopic mucosa can be seen without any cave or protruding, in normal color, glossy.(2) Cases of atypical hyperplasia group: atypical hyperplasia reported by the endoscopicbiopsy pathological mechanism, and then cases confirmed as canceration except thoseevidenced by endoscopic mucosal resection or sub mucosal dissection;(3) Cases ofearly gastric cancers group:1) cancer confirmed by endoscopic pathology with anoperation limit cases, and2) tissue slices pathology proved as canceration after theendoscopic mucosal resection or surgery operations but limited to mucous membrane orsubmucosal layer and high grade intraepithelial neoplasia no matter how the lymphnode metastasis is.(4) Cases of advanced gastric carcinoma group:1) cases of cancerwith an operation limit in endoscopic pathology diagnosis, and2) canceration is notlimited to submucosal proved by surgery operation pathology. Excluding standards:(1)one has a malignant tumor history,(2) one has an emergency operation,(3) whendistant metastases or infiltration of adjacent organs are found before an operation,(4)one can not be operated if during one’s trimester of pregnancy, or one is critically illand in any other cases, and (5) one is coagulation abnormal.3、81patients with EGC (44for endoscopic mucosal resection,37for surgicaltreatment) from the year2001to2011in the Central hospital of Dalian were collectedfor this analysis.And compared with two groups of operation time, operation expense,length of stay in hospital, operative complications, follow-up and so on.Results:1、For image resolution, magnifying NBI and magnifying chromoendoscopy weresignificantly superior tomagnifying conventional endoscopy in morphology, pit patternand blood capillary form (P <0.01), andmagnifying NBI was significantly superior tomagnifying chromoendoscopy in blood capillary form (P <0.01). IV, V1,and VI type ofgastric pit pattern were detected in14cases,43cases, and17cases in patients with highgradeintraepithelial neoplasia, respectively. V1and VI type of gastric pit pattern weredetected in9cases and39cases inpatients with early gastric cancer, respectively. Thepresence of irregular minute vessels and variation in the caliberof vessels was found in109cases. The accuracy, sensitivity, specificity, false positive rate and false negativerate fordiagnosis of early gastric cancer and precancerous gastric lesions were68.9%,95.1%,63.1%,24.5%, and32.4%forconventional endoscopy,93.6%,92.7%,94.5%,5.7%, and6.9%for magnifying NBI, and91.3%,88.6%,93.2%,13.2%,and21.48%for magnifying chromoendoscopy, respectively.2、The positive expression percentages of Galectin-3protein in gastric canceroustissues is72.6%, and the positive expression percentages of high and middle, and lowanaplastic carcinoma are73.3%and71.4%respectively. There is no significantdifference compared between the two groups (p>0.05); The positive expression in TNMperiod I+II is60.7%, while in TNM period III+IV is80.4%, there is great differencebetween these two groups (p<0.05); the positive expression of lymph node metastasisand no lymph node metastasis are94.1%and61.8%respectively, there is greatdifference between this two groups (p<0.05). There is no obvious difference (p>0.05)between the normal gastric mucosa group (30.0%) and atypical hyperplasia group(44.0%) of the positive expression of Galectin-3protein, however it is distinctly lowerthan that of early gastric cancers group (64.3%)(p<0.05) and advanced gastriccarcinoma group (82.6%)(p<0.01). There is no obvious difference (p>0.05) betweenatypical hyperplasia group (44.0%) and early gastric cancers group (64.3%) of thepositive expression of Galectin-3protein, however it is evidently lower than that ofadvanced gastric carcinoma group (82.6%)(p<0.01). There is no obvious difference(p>0.05) between early gastric cancers group (64.3%) and advanced gastric carcinomagroup (82.6%) of the positive expression of Galectin-3protein.The positive expression of P27protein in gastric cancerous tissues is35.2%, andthe positive expression percentages of high and middle, and low anaplastic carcinomaare43.3%and23.8%respectively. There is no significant difference compared betweenthe two groups (p>0.05); The positive expression in TNM period I+II is39.3%, whilein TNM period III+IV is30.4%, there is no obvious difference between this twogroups (p>0.05); the positive expression of lymph node metastasis and no lymph nodemetastasis are58.8%and23.5%respectively, there is great difference between thesetwo groups (p<0.05). There is no obvious difference (p>0.05) between the normalgastric mucosa group (85.0%) and atypical hyperplasia group (72.0%) of the positiveexpression of P27protein, however it is distinctly higher than that of early gastriccancers group (42.6%) and advanced gastric carcinoma group (26.0%)(p<0.01). Thepositive expression of P27protein in atypical hyperplasia group (72.0%) is distinctivelyhigher than that of early gastric cancers group (42.6%)(p<0.05)and advanced gastriccarcinoma group (26.0%)(p<0.01); There is no obvious difference (p>0.05) betweenearly gastric cancers group (42.6%) and advanced gastric carcinoma group (26.0%) ofthe positive expression of P27protein. The positive expression of mRNA of Galectin-3in the cases of normal gastricmucosa group is not less than that of cases of atypical hyperplasia group and cases ofearly gastric cancers group. There is no obvious difference between atypical hyperplasiagroup and early gastric cancers group, however both of them are distinctly lower thanthat of advanced gastric carcinoma group; the positive expression of mRNA of P27innormal gastric mucosa group, atypical hyperplasia group, early gastric cancers groupand advanced gastric carcinoma group shows a decreasing trend. The expressioninspection results of mRNA in Galectin-3and P27are respectively in accordance withthe realities of their protein expressions in tissues.3、For endoscopic mucosal resection group, the operation time, operation expense,length of stay in hospital, postoperative anus exhaust time and independent activitytime under the bed were all less than surgical resection group, and there was asignificant difference between the two groups (P <0.05).About operative complicationsoccurring rate and postoperative painkillers utilization rate, endoscopic mucosalresection group were lower than those of the surgical resection group, and there was asignificant difference between them (P <0.05). Follow-up of both two groups did nothappen with residue, local recurrence and heterochrony lesions. The anesthesia andoperative approach, injury of organs as well as working ability, veneous drug therapy,physical condition and so on postoperative life quality evaluation, endoscopic mucosalresection group was better than surgical group.Conclusion:1、 This study demonstrates that magnifying NBI is superior toconventionalendoscopy in the diagnosisof early gastric cancer and precancerous gastriclesions, and can be used for screening early malignancies of thestomach.2、The positive expression percentages of mRNA and Galectin-3proteins arerelated to the occurrences and development of gastric carcinoma, where the normalgastric mucosa group and atypical hyperplasia group are obviously lower than earlygastric cancers group and advanced gastric carcinoma group, where it is notsignificantly related to the TNM periods or the differentiation carcinoma, where it isrelated to lymph node metastasis, and it is probably to be an important index ofevaluation prognosis for early gastric cancers screening and judgments of lymph nodemetastasis in early gastric cancer.The positive expression percentages of mRNA and P27proteins are related to theoccurrences and development of gastric carcinoma, where the normal gastric mucosa group and atypical hyperplasia group are obviously higher than early gastric cancersgroup and advanced gastric carcinoma group, where it is likely related to the TNMperiods and the differentiation carcinoma, where it is related to lymph node metastasis,and its expression reduction of P27is probably to be an effective indicator of evaluationprognosis for early gastric cancers screening and judgments of lymph node metastasis inearly gastric cancer and lymph node metastasis.The expression of Galectin-3and P27protein are opposite to that of mRNA in thedevelopment of gastric cancers. There is no significant difference between the positiveexpressions of Galectin-3and P27, but inspections of both Galectin-3and P27at thesame time can provide more bases for the gastric cancers diagnosis.3、Endoscopic mucosal resection treatment for EGC is safe, feasible, minimallyinvasive and effective.