1.The Prognostic Significance Of The Treatment Response Of Regional Lymph Nodes And The Refinement Of Current TNM Staging System In Locally Advanced Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy 2.The Safety And Efficacy Of Radical Surgery Fo

Part Ⅰ:The prognostic significance of the treatment response of regional lymph nodes and the refinement of current TNM staging system in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapyBackgroundCurrent TNM staging system has been used the same category definition for both rectal cancer patients with and without neoadjuvant chemoradiotherapy(NCRT).Because of the total number of lymph nodes and the number of positive lymph nodes retrieved afterNCRT significantly decreased,therefore,current ypTNM stage,especially ypN stage does not well predict patients’ survival afterNCRT.Tumor cells in the lymph nodes will also display different degrees of treatment response after NCRT,Whether tumor regression in lymph nodes(LRG)may improve the prediction of patients’ survival has not been well studied.In this study,we investigated the progonostic significance of the LRG,and then tried to use LRG to modify the current ypN stage and ypTNM stage.MethodsIn total,358 patients with rectal cancer and received NCRT followed by radical resection were recruited from January 2004 to December 20 1 5,and the median follow-up time was 57.5 months.The pathologist reviewed the pathological slices of the enrolled patients,evaluated the LRG of the patients.And we further analyzed the prognostic significance of the LRG on rectal patients.Main outcome measure was patients’ disease-free survival(DFS).ResultsIn univariate analysis,factors associated with DFS were ypN stage,number of negative lymph nodes(NLN),lymph node ratio(LNR),maximum of LRG(LRGmax),sum score of LRG(LRGsum),LRG ratio(average value of LRGsum)and M-NLRG(modified ypN stage by combining LRGmax and LNR).The results of subgroup analysis showed that there was no significant difference in 5-year DFS between ypN1 stage and ypN2 stage(53.9%vs 47.7%,P=0.321),but the LRG related prognostic index could distinguish the prognosis of each subgroup significantly.In a multivariate Cox regression analysis,TRG and M-NLRG(P<0.001 and P=0.022,respectively)were significantly associated with DFS,whereas ypT stage and ypN stage were not.The estimated 5-year DFS was 86.6%,60.3%and 36.4%for patients with M-NLRG-0,M-NLRG-1,M-NLRG-2 respectively(P<0.001).Significant difference was obtained among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system(P<0.001).And the modified TNM staging system could better predict the prognosis of patients than current ypTNM staging system.ConclusionsLRG is an important prognostic factor for rectal cancer patients who have received NCRT,and the current ypN stage cannot accurately predict the prognosis of rectal cancer patients after NCRT.In this study,the new prognostic index,M-NLRG,could better predict the prognosis of rectal cancer patients than current ypN stage.The modified ypTNM staging system in combination with LRGmax,LNR and TRG could improve DFS prediction in each subset of patients.Part Ⅱ:The safety and efficacy of radical surgery for locally advanced rectal cancer patients after modified total neoadjuvant therapyBackgroundTotal neoadjuvant therapy(TNT)is a new treatment strategy for locally advanced rectal cancer.The purpose of TNT is to minimize tumor,eliminate potential distant metastases,improve the effectiveness of neoadjuvant therapy,and improve the long-term survival of patients by standard systemic chemotherapy before surgery.However,because of high treatment intensity and high incidence of side effects,the TNT treatment may lead to an increased incidence of postoperative complications.Furthermore,the TNT treatment may have the possibility of over-treatment in some patients.Therefore,some researchers have proposed a modified TNT(mTNT)treatment strategy.For locally advanced rectal cancer patients with a high risk of recurrence,such as cT4,regional lymph node metastasis,mesorectal fascia(MRF)involvement,lateral lymph node metastasis(LLNM),extramural venous invasion(EMVI),etc.,individualized preoperative treatment should be carried out.Systemic chemotherapy is performed before surgery to shrink the tumor as much as possible to ensure the RO resection of the tumor.At the same time,it avoids excessively long neoadjuvant treatment and waiting time for surgery,and to a certain extent avoids over-treatment before surgery.The aim of this study was to analyze the clinical.pathological data of patients with locally advanced rectal cancer who underwent modified total neoadjuvant therapy,and to evaluate the safety and efficacy of radical surgery after modified total neoadjuvant therapy.MethodsThe clinical-pathological data of 30 locally advanced rectal cancer patients who underwent modified total neoadjuvant therapy followed by radical resection was retrospectively analyzed.The surgical procedure,postoperative complications,tumor regression grade,tumor downstaging and prognosis were analyzed.ResultsThe 30 patients included 24 males and 6 females with a median age of 55.5 years.All patients underwent radical surgery after neoadjuvant therapy,and 26(86.7%)patients underwent laparoscopic surgery.Fourteen patients received low anterior resection,14 patients received abdominal perineal resection,and the other 2 patients received Hartmann procedure.All patients achieved R0 resection with a median operative time 220 minutes(120-315 minutes)and a median intraoperative blood loss 200 ml(20-800 ml).The morbidity of postoperative complications was 20%(6/30),including dysuria in 2 patients(6.67%),delayed healing of perineal incision in 2 patients(6.67%),intestinal obstruction in 1 patient(3.33%)and pelvic hemorrhage in 1 patient(3.33%).Only 1(3.3%)patient needed surgery treatment again due to the postoperative complications.The median time to first flatus after surgery was 3 days(2-5 days)and the median postoperative hospital stay was 8 days(5-16 days).Postoperative pathological results showed that 15 patients(50.0%)had severe tumor regression,including 4 patients(13.3%)achieved pathological complete response(pCR),12 patients(40.0%)had moderate tumor regression,and 3 patients(10.0%)had minor tumor regression.75.0%and 65.0%patients achieved downstaging of tumor T stage and N stage,respectively.There were only 2 patients appeared distant metastasis,and no patient had local recurrence.ConclusionModified total neoadjuvant therapy(mTNT)didn’t increase the morbidity of postoperative complication.And this treatment strategy provided a safe and effective treatment option for locally advanced rectal cancer patients.