The Diagnostic Value Of NBI-ME In Early Esophageal Squamous Cell Cancer And Precancerous Lesions And The Study Of The Expression Of BNIP3/Beclin-1 In The Occurrence Of Esophageal Cancer

Esophageal cancer is a common gastrointestinal tumor in human and the lymph node metastasis occurres in earlier period.The majority of the patients have been in late stage when they were diagnosed and the 5-year survival rate is less than 20% and the prognosis is poor,while the 5-year survival rate could reach 95% if they are treated in early stage that was limited in mucosa or submucosa.So early detection and early treatment show a great significance for esophageal cancer.But lesions of early esophageal cancer are not obvious and the diagnosis are difficult.The lesions are easily missed in ordinary white light endoscopic and the missed diagnosis rate could up to 40%.With the development of endoscopic techniques,lugol chromoendoscopy with pink-color sign was used to esophageal which has greatly increased the detection rate of early esophageal cancer,but there are also many disadvantages in iodine staining(such as chest pain,heartburn,etc.),but the problems that caused by chemical dyes could be avoided narrow-band imaging which can increase the contrast and sharpness of mucosal epithelium and submucosal vascular.Japanese scholar Inoue Ching Yang who is the first person that proposed the IPCL type by using magnifying endoscopy(ME)to observe the morphological changes of esophageal intrapapillary capillary loop(IPCL)which can distinguish benign esophageal lesions from malignant lesions,judge the scope of lesions and the depth of invasion.Using NBI-ME to observe the IPCL type to diagnoe esophageal cancer and precancerous lesions has become a hotspot at present.It is still a controversial topic about whether NBI-ME can replace iodine staining,so it is important to discuss the diagnostic value of NBI-ME in early esophageal cancer and precancerous lesions.The development of esophageal cancer is a complex process with multi-gene mutation and multi-step.It is an effective method to look for a sensitive and specific indicator to diagnose in earlier period,judge the prognosis and reach a long-term survival.People have been linked up tumor with cell autophagy and realized that the autophagy ability of tumor cells was lower than normal since the late 1970 s.The formation and regulation of autophagy is an extremely complex and multi-step process.HIF-1α / BNIP3 / Beclin-1 is known as an important signaling pathway that upregulate autophagy in hypoxic conditions.Beclin-1 interacts with Bcl-XL and Bcl-2 through BH3 domains under physiological conditions,but BNIP3 can be activated by the activation HIF-1 to cause Beclin-1 and Bcl-XL and Bcl-2 being dissociated under hypoxia conditions that can activate autophagy by releasing Beclin-l.It has been found that autophagy is closely related to the development of gastrointestinal tumors.It may have an important clinical value to discuss the expression of BNIP3/Beclin-1 in the occurrence of esophageal cancer.This experiment is divided into two parts,the first part is to discuss the diagnostic value of NBI-ME for early esophageal cancer and precancerous lesions,and the second part is to discuss the expression of BNIP3/Beclin-1 in the occurrence of esophageal cancer.Part One The diagnostic value of NBI-ME in early esophageal squamous cell cancer and precancerous lesionsObjective: To discuss the diagnostic value of NBI-ME in early esophageal squamous cell cancer and precancerous lesions and the consistency of IPCL types and pathological diagnosis.Methods: From March 2015 to January 2016 in the gastrointestinal endoscopy Endoscopy Center of Second Hospital of Hebei Medical University,35 patients(39 lesions)were enrolled into this study and performed with NBI-ME and lugol iodine staining to observe the morphology of lesions and made diagnosis immediately.Then the lesions were targeted biopsy or treated by EMR/ESD and checked by pathological examination to compare the diagnostic value of two staining methods and compare the consistency of IPCL types and pathological diagnosis.Result:1 The 39 lesions were found by NBI and iodine staining and all of them were confirmed by histopathology.There were 7 cases of inflammation,10 cases of low grade intraepithelial neoplasia,14 cases of high grade intraepithelial neoplasia and 8 cases of esophageal cancer.The sensitivity,specificity,positive predictive value and negative predictive value of NBI-ME and LCE-PS to esophageal cancer and precancerous lesions were 95.4% and 86.4%,66.7% and 80%,81% and 87.5%,81% and 87.5% respectibely.There were no significant differences between all of them(P > 0.05).2 92.3% of IPCL type III were mainly inflammation and low-grade intraepithelial neoplasia,69.2% of IPCL typeIV were mainly high-grade intraepithelial neoplasia.61.2% of IPCL typeV were major invasive esophageal cancer,.The consistency analysis of IPCL classification and pathological relationship is that the Kappa value was 0.615.Conclusion:1 NBI-ME and iodine staining have a considerable value in the diagnosis in early esophageal squamous cell cancer and precancerous lesions and iodine staining can be replaced by NBI-ME in patients who are not suitable for iodine staining.2 IPCL Types in NBI-ME have a good consistency with pathological.It is helpful to determine depth of invasion of esophageal cancer and assist in selecting the appropriate treatment.Part II The study of the expression of BNIP3/Beclin-1 in the occurrence of esophageal cancerObjective: HIF-1α/BNIP3/Beclin-1 is known as an important signaling pathway that upregulate autophagy in hypoxic conditions.Our purpose is to explore the expression of BNIP3 and Beclin-1 in the occurrence of esophageal cancer.Methods: The expression of BNIP3 and Beclin-1 were detected by immuno histochemistry in 24 cases of intraepithelial neoplasia patients and 8 cases of invasive esophageal cancer and 10 cases of normal esophageal tissues to analysis the diversification of BNIP3/Beclin-1 in the occurrence of esophageal cancer.Result:1 The immunohistochemistry showed that the expression of BNIP3 mainly located in the cytoplasm,and partially expressed in the nucleus.BNIP3 expressed as a pale yellow in normal and invasive esophageal cancer tissue,bue it increased significantly in intraepithelial neoplasia tissues as brownish yellow.The IOD value of BNIP3 in normal esophageal group is 21653.38 ± 2493.79,in intraepithelial neoplasia group is 36020.16 ± 3689.70,in invasive esophageal cancer group is 10448.31 ± 2158.00.The expression levels of BNIP3 in each group are as follows: intraepithelial neoplasia group > control group > invasive esophageal cancer group.The expression of BNIP3 had a significant differential in normal group,intraepithelial neoplasia group and invasive esophageal(P <0.001).There was a significantly differential between any two groups(P < 0.01).2 The immunohistochemistry showed that the expression of Beclin-1 mainly located in the cytoplasm.Beclin-1 expressed as a pale yellow in normal and invasive esophageal cancer tissue,bue it increased significantly in intraepithelial neoplasia tissues as brownish yellow.The IOD value of Beclin-1 in normal esophageal group is 12172.60±2214.48,in intraepithelial neoplasia group is 25719.82±2038.59,in invasive esophageal cancer group is 3079.05±1457.10.The expression levels of Beclin-1 in each group are as follows: intraepithelial neoplasia group > control group > invasive esophageal cancer group.The expression of Beclin-1 had a significant differential in normal group,intraepithelial neoplasia group and invasive esophageal(P < 0.001).There was a significantly differential between any two groups(P < 0.01).Conclusion: The expression of BNIP3 and Beclin-1 were involved in the occurrence of esophageal cancer.The expression of BNIP3 and Beclin-1 in intraepithelial neoplasia group was significantly increased compared with normal control group,while in invasive esophageal cancer group was decreased.It may contribute to the early diagnosis in detecting the expression of BNIP3 and Beclin-1.