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Application Of Intrathoracic Anastomosis In Esophageal Squamous Lymphadenectomy And Cancer - Related Gene Mutations And Human Papillomavirus Infection

Posted on:2014-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:L L ShaoFull Text:PDF
GTID:2134330434970791Subject:Oncology
Abstract/Summary:PDF Full Text Request
Esophageal cancer is one of the most fatal diseases in the world, and the sixth leading cause of cancer-related death worldwide. Esophagectomy is still the preferred initial treatment for patients with this disease. Three-field (Neck, chest and abdomen) Lymph Node Dissection (3FLND) has been increasingly used in Asia recently, because of the well local control rates and satisfying outcome. Compared with traditional surgery methods for esophageal cancer,3FLND increase the surgical trauma and risk. In medical centers with large volume, operative mortality and complications can be controlled in the acceptable level, but anastomotic leakage, one of the most typical and life-threatening morbidities, is hard to predict and prevent and should not be ignored. Once anastomotic leakage occurred, patients need much longer time for fasting and drainage to recovery, complicating other serious diseases and may become life-threatening. The anastomosis was performed in3FLND in the neck routinely, which might be the cause of high incidence of anastomotic leakage after operation. This study aims to introduce initial experience of intrathoracic anastomosis after resection of esophageal cancer with3FLND, and to verify its clinical value.During2009.1-2011.12, Fudan University Cancer Center had carried out214cases of esophagectomy with3FLND,33cases with intrathoracic anastomosis and181cases with cervical anastomosis. Clinical data of postoperative outcomes and short-term survival from these two groups of patients were collected and analyzed. Conventional statistical methods propensity score matching ways were used to analyze separately.The results showed that the anastomotic leakage rate was significantly lower in the intrathoracic anastomosis group (1/33,3.03%VS37/181,20.44%, p=0.016); the median hospital stay was shorter than in the cervical anastomosis group [11(8-76) vs14(4-128) days, p=0.001]. The median follow-up period was26months and there was no difference of survival rates between the two groups (p=0.868). Age, sex ratio, history, operative time, blood loss, number of lymph node dissection and TNM stage between the two groups were similar. After we performed propensity score matching, intrathoracic anastomosis was also associated with less incidence of leakage (hazard ratio=0.098,95%CI=0.011-0.833, p=0.033), and with no compromise on short-term outcome. We also found manual anastomosis, only locating in the the neck, significantly reduced cervical anastomotic fistula (HR=0.431,95%CI=0.187-0.989, P=0.047). The anastomosis location and anastomotic method affected the incidence of anastomotic leakage independently.Our initial experience suggested that with3FLND intrathoracic anastomosis after resection of esophageal cancer may reduce the incidence of anastomotic leakage with no compromise on short-term outcome, and when anastomosis need to be performed in the neck, manual suture is the better choice. Esophageal cancer is one of the most common cancers in the world, with poor prognosis, and there is no breakthrough new treatment found in recent years. Tumors are the result of the combined effect of genetic and environmental factors. Esophageal cancer is often associated with irritating diet, low-income and alcohol or tobacco abuse, and has obvious regional differences on distribution. There are few studies on genetic variations and viral infections of esophageal squamous cell carcinoma (ESCC). By analyzing the relationship between mutations of some tumor-related gene or the infection of human papillomavirus (HPV) and the clinicopathological data, this study aim to investigate the possible role of these factors in ESCC.Variations of EGFR, KRAS, PIK3CA and PTEN gene were detected in120fresh tissues of ESCC using polymerase chain reaction (PCR) and direct sequencing technique.The existence of13high-risk subtypes of HPV in the tumor tissue was detected by the use of HPV DNA genomic probe. Clinical data of the120patients were collected and analyzed with experimental results.We found neither EGFR nor KRAS gene mutations in the tissues of ESCC. Missense mutations (E542K, E545K, H1047R/L) were identified in exon9and exon20of PIK3CA gene from7patients (5.8%), and they have been previously reported as hotspot mutations. point mutations (i.e., I224M, R234W, F341V) in PTEN gene were found from20patients (16.7%). HPV plasmid was identified in53cases (44.2%), the most common of which was subtype16; Infection rate of HPV was significantly higher in the poorly differentiated tumors than in highly or moderately differentiated.This study suggested that TKI molecular targeted drugs have limited efficacy in patients with ESCC because of the low mutation rate or EGFR and KRAS gene. PIK3CA gene mutations existed in ESCC indicated that PIK3CA-AKT pathway targeted therapy might be useful for these patients. Higher prevalence of HPV in esophageal squamous cell carcinoma, and related to poorly differentiated tumors, suggested there was a certain correlation between HPV and ESCC.
Keywords/Search Tags:Esophageal cancer, Three-field Lymph Node Dissection, Anastomotic leak, Propensity matchingesophageal squamous cell carcinoma, gene mutation, human papillomavirus
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