Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms:A Chinese multicenter study of 12-year experience

BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.

Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality worldwide.Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and recurrence.CASE SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old man.He received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also disappeared.CONCLUSION pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+rectal cancer:Istanbul R-02 phase II randomized study

Radiation therapy(RT)is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer(LARC):short-course RT(SC-RT)alone or long-course RT(LC-RT)with concurrent fluorouracil(5-FU)chemotherapy.The Phase II single-arm KROG 11-02 study using intermediate-course(IC)(33 Gy(Gray)/10 fr(fraction)with concurrent capecitabine)preoperative chemoradiotherapy(CRT)demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT.The current trial aim to compare the pathological/oncological outcomes,toxicity,and quality of life results of LC-CRT and IC-CRT in cases of LARC.The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group.Concurrent chronomodulated capecitabine(Brunch regimen)1650 mg/m2/daily chemotherapy treatment was applied in both groups.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module(EORTC QLQ-CR29)was administered at baseline and at three and six months after CRT.A total of 60 patients with LARC randomized to receive IC-CRT(n=30)or LC-CRT(n=30)were included in this phase II randomized trial.No significant difference was noted between groups in terms of pathological outcomes,including pathological response rates(ypT0N0-complete response:23.3%vs.16.7%,respectively,and ypT0-2N0-downstaging:50%for each;p=0.809)and Dworak score-based pathological tumor regression grade(Grade 4-complete response:23.3 vs.16.7%,p=0.839).The 5-year overall survival(73.3 vs.86.7%,p=0.173)rate was also similar.The acute radiation dermatitis(p<0.001)and any hematological toxicity(p=0.004)rates were significantly higher in the LC-CRT group,while no significant difference was noted between treatment groups in terms of baseline,third month,and sixth month EORTC QLQ-CR29 scores.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

Transanal Endoscopic Microsurgery (TEM) for Rectal Neoplasms

Introduction: The abdominal approach for the treatment of rectal tumors is associated with a considerable rate of morbidity. Transanal Endoscopic Microsurgery (TEM) is an alternative technique that is less invasive than radical surgery, and therefore has a lower associated morbidity. Moreover, with proper patient selection, TEM presents oncological outcomes comparable to radical surgery. The aim of this study is to review our results obtained with TEM and discuss its role in the treatment of malignant rectal lesions. Patients and Methods: A prospective descriptive study from June 2008 until February 2011. The indications for TEM were: early rectal neoplastic lesions (T1N0M0) with good prognostic factors;neoplastic lesions in more advanced stages in selected patients (high surgical risk, refusal of radical surgery or stoma, and palliative intention). Results: Resection by TEM was performed on 19 patients. The average hospital stay was 5.7 days with an associated morbidity of 16.7%. R0 resection was 88.8%. During the follow-up of 15 (3 - 31) months, no recurrence has been shown. Conclusions: TEM is a safe and effective procedure for the treatment of selected early malignant rectal lesions and is associated with low morbidity. It is a therapeutic strategy based on a multidisciplinary team, careful patient selection, an audited surgical technique and a strict follow-up protocol.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review

BACKGROUND Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide.About 5%-10%of patients are diagnosed with locally advanced rectal cancer(LARC)on presentation.For LARC invading into other structures(i.e.T4b),multivisceral resection(MVR)and/or pelvic ex-enteration(PE)remains the only potential curative surgical treatment.MVR and/or PE is a major and complex surgery with high post-operative morbidity.Minimally invasive surgery(MIS)has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies,but there is little evi-dence on its use in MVR,especially so for robotic MVR.This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023.Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR,or stage 4 disease with resectable systemic metastases.Pa-tients who underwent curative MVR for locally recurrent rectal cancer,or me-tachronous rectal cancer were also included.Exclusion criteria were patients with systemic metastases with non-resectable disease.All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery.Complex sur-gery was defined based on technical difficulty of surgery(i.e.total PE,bladder-sparing prostatectomy,pelvic lymph node dissection or need for flap creation).Our primary outcomes were the margin status,and complication rates.Cate-gorical values were described as percentages and analysed by the chi-square test.Continuous variables were expressed as median(range)and analysed by Mann-Whitney U test.Cumulative overall survival(OS)and recurrence-free survival(RFS)were analysed using Kaplan-Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.RESULTS A total of 46 patients were included in this study[open MVR(oMVR):12(26.1%),miMVR:36(73.9%)].Patients’American Society of Anesthesiologists score,body mass index and co-morbidities were comparable between oMVR and miMVR.There is an increasing trend towards robotic MVR from 2015 to 2023.MiMVR was associated with lower estimated blood loss(EBL)(median 450 vs 1200 mL,P=0.008),major morbidity(14.7%vs 50.0%,P=0.014),post-operative intra-abdominal collections(11.8%vs 50.0%,P=0.006),post-operative ileus(32.4%vs 66.7%,P=0.04)and surgical site infection(11.8%vs 50.0%,P=0.006)compared with oMVR.Length of stay was also shorter for miMVR compared with oMVR(median 10 vs 30 d,P=0.001).Oncological outcomes-R0 resection,recurrence,OS and RFS were comparable between miMVR and oMVR.There was no 30-d mortality.More patients underwent robotic compared with laparoscopic MVR for complex cases(robotic 57.1%vs laparoscopic 7.7%,P=0.004).The operating time was longer for robotic compared with laparoscopic MVR[robotic:602(400-900)min,laparoscopic:Median 455(275-675)min,P<0.001].Incidence of R0 resection was similar(laparoscopic:84.6%vs robotic:76.2%,P=0.555).Overall complication rates,major morbidity rates and 30-d readmission rates were similar between la-paroscopic and robotic MVR.Interestingly,3-year OS(robotic 83.1%vs 58.6%,P=0.008)and RFS(robotic 72.9%vs 34.3%,P=0.002)was superior for robotic compared with laparoscopic MVR.CONCLUSION MiMVR had lower post-operative complications compared to oMVR.Robotic MVR was also safe,with acceptable post-operative complication rates.Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

Feasibility and limitations of combined treatment for lateral pelvic lymph node metastases in rectal cancer

Colorectal cancer ranks among the most commonly diagnosed cancers globally,and is associated with a high rate of pelvic recurrence after surgery.In efforts to mitigate recurrence,pelvic lymph node dissection(PLND)is commonly advocated as an adjunct to radical surgery.Neoadjuvant chemoradiotherapy(NACRT)is a therapeutic approach employed in managing locally advanced rectal cancer,and has been found to increase the survival rates.Chua et al have proposed a combination of NACRT with selective PLND for addressing lateral pelvic lymph node metastases in rectal cancer patients,with the aim of reducing recurrence and improving survival outcomes.Nevertheless,certain studies have indicated that the addition of PLND to NACRT and total mesorectal excision did not yield a significant reduction in local recurrence rates or improvement in survival.Consequently,meticulous patient selection and perioperative chemotherapy may prove indispensable in ensuring the efficacy of PLND.

Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

Impact of technology on indications and limitations for transanal surgical removal of rectal neoplasms

Transanal surgery has and continues to be well accepted for local excision of benign rectal disease not amenable to endoscopic resection. More recently, there has been increasing interest in applying transanal surgery to local resection of early malignant disease. In addition, some groups have started utilizing a transanal route in order to accomplish total mesorectal excision(TME) for more advanced rectal malignancies. We aim to review the role of various transanal and endoscopic techniquesin the local resection of benign and malignant rectal disease based on published trial data. Preliminary data on the use of transanal platforms to accomplish TME will also be highlighted. For endoscopically unresectable rectal adenomas, transanal surgery remains a widely accepted method with minimal morbidity that avoids the downsides of a major abdomino-pelvic operation. Transanal endoscopic microsurgery and transanal minimally invasive surgery offer improved visualization and magnification, allowing for finer and more precise dissection of more proximal and larger rectal lesions without compromising patient outcome. Some studies have demonstrated efficacy in utilizing transanal platforms in the surgical management of early rectal malignancies in selected patients. There is an overall higher recurrence rate with transanal surgery with the concern that neither chemoradiation nor salvage surgery may compensate for previous approach and correct the inferior outcome. Application of transanal platforms to accomplish transanal TME in a natural orifice fashion are still in their infancy and currently should be considered experimental. The current data demonstrate that transanal surgery remains an excellent option in the surgical management of benign rectal disease. However, care should be used when selecting patients with malignant disease. The application of transanal platforms continues to evolve. While the new uses of transanal platforms in TME for more advanced rectal malignancy are exciting, it is important to remain cognizant and not sacrifice long term survival for short term decrease in morbidity and improved cosmesis.

Ratio of metastatic lymph nodes is more important for rectal cancer patients treated with preoperative chemoradiotherapy

AIM:To evaluate the predictive value of the lymph node(LN) ratio(LNR,number of metastatic LNs/ examined LNs) for recurrence in patients with rectal cancer and to compare its applicability according to preoperative chemoradiotherapy(PCRT).METHODS:From 2000 to 2009,967 patients with metastatic LNs after curative resection for locally advanced rectal cancer were identified.Patients were categorized according to PCRT(PCRT vs No PCRT).The cut-off LNR was determined based on the p N1 vs p N2 when the recommended number of LNs was harvested.The 5-year recurrence-free survival(RFS) rates using the Kaplan-Meier method were compared according to p/yp N stage and the LNR in each group.RESULTS:Among patients with the same p/yp N stage,the 5-year RFS rate differed according to the LNR.In addition,the 5-year RFS rate was significantly different between p N and LNR groups in patients with No PCRT.In PCRT group,however,only LNR was associated with prognosis.On multivariate analysis,both p N and LNR were significant independent prognostic factors for 5-year RFS in the No PCRT group.In the PCRT group,only LNR category was found to be associated with RFS(HR = 2.36,95%CI:1.31-3.84,and P = 0.001).CONCLUSION:The LNR is an important prognostic predictor of RFS in rectal cancer patients especially treated with PCRT.Current p N categories could not discriminate between prognostic groups of RFS after PCRT.

Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer

Introduction:Preoperative chemoradiotherapy(CRT),followed by total mesorectal excision,has become the standard of care for patients with clinical stages II and III rectal cancer.Patients with pathologic complete response(pCR) to preoperative CRT have been reported to have better outcomes than those without pCR.However,the factors that predict the response to neoadjuvant CRT have not been well defined.In this study,we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer.Methods:A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT,followed by curative surgery,between 2005 and 2013 were included.Patients were divided into two groups according to their responses to neoadjuvant therapy:the pCR and non-pCR groups.The clinical parameters were analyzed by univariate and multivariate analyses,with pCR as the dependent variable.Results:Of the 323 patients,75(23.2%) achieved pCR.The two groups were comparable in terms of age,sex,body mass index,tumor stage,tumor location,tumor differentiation,radiation dose,and chemotherapy regimen.On multivariate analysis,a pretreatment carcinoembryonic antigen(CEA) level of <5 ng/mL[odds ratio(OR) = 2.170,95%confidence interval(CI) = 1.195-3.939,P = 0.011]and an interval of >7 weeks between the completion of chemoradiation and surgical resection(OR = 2.588,95%CI = 1.484-4.512,P = 0.001) were significantly associated with an increased rate of pCR.Conclusions:The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR.These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

Introduction: Multimodality therapy, including preoperative chemoradiotherapy(CRT) and total mesorectal excision(TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy(CCRT) involving XELOX regimen(oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.Methods: We randomly assigned patients to the TME group(TME without preoperative CCRT) or CCRT + TME group(TME with preoperative CCRT). The primary endpoint was disease-free survival(DFS); the secondary endpoints were overall survival(OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.Results: A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 %(P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 %(P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT +TME groups were 71.3 % and 70.0 %(P = 0.849), respectively. In the TME group, 16(17.0 %) patients were proven to have p TNM stage I disease after surgery. In the CCRT + TME group, 32(35.6 %) patients achieved a pathologic complete response(p CR).Conclusions: Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high p CR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.

Long-term outcomes in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy and curative resection

Objective： For patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy（NCRT）, significant pathological response of the primary tumor has been proposed to identify candidates for organ preservation. However, this does not address metastatic lymph nodes in the mesorectum. The aim of this study was to assess the incidence of lymph node metastases in ypT0 patients treated with NCRT and curative resection and to explore risk factors associated with survival.Methods： This was a retrospective study of patients with ypT0 rectal cancer after NCRT and curative resection at a tertiary care center in China from 2005 to 2014.Results： A total of 60（18.6%） patients who underwent surgery after NCRT and achieved ypT0 were enrolled in this study; one patient was excluded owing to lack of follow-up. Of these 59 patients, lymph node metastases were found in the mesorectum（ypT0N＋） in eight（13.6%） patients. After a median follow-up of 52 months, 5-year recurrence-free survival（82.7% vs. 62.5%, P=0.014） and overall survival（OS）（90.9% vs. 70.0%, P=0.032） were much higher in ypN0 than yp N＋ patients. Multivariate analyses showed that ypN＋ status（P=0.009） and perioperative blood transfusion（BT）（P=0.001） were significantly independent risk factors associated with recurrence; however, no factor was correlated with 5-year OS.Conclusions： Patients with ypT0N0 rectal cancer can achieve excellent long-term outcomes; however, positive lymph nodes or tumor deposits can still be found in 13.6% of ypT0 patients. Nodal positivity in the mesorectum and perioperative BT are independent risk factors for recurrence.

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer:The debate continues

Rectal carcinoma represents the 30% of all colorectal cancers, with about 40000 new cases/years. In the past two decades, the management of rectal cancer has made important progress, highlighting the main role of a multimodality strategy approach, combining surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neoadjuvant chemoradiotherapy, based on fluoropyrimidine(5-FU) continuous infusion, is considered the standard in locally advanced rectal carcinoma. The aim is to reduce the incidence of local recurrence and to perform a conservative surgery. To improve these purposes different drugs combination have been tested in the neo-adjuvant setting. At American Society of Clinical Oncology 2014 an important abstract was presented focusing on the role of adding oxaliplatin to concomitant treatment, in patients with locally advanced rectal carcinoma. Rodel et al reported on the CAO/ARO/AIO-04 randomized phase Ⅲ trial that compared standard treatment with 5-FU and radiation therapy, to oxaliplatin plus 5-FU inassociation with radiation therapy. The addition of oxaliplatin to the neo-adjuvant treatment has been shown to improve disease-free survival from 71.2% to 75.9%(P = 0.03). This editorial was planned to clarify the optimal treatment in patients with locally advanced rectal cancer, considering the results from CAO/ARO/AIO-04 study.

Impression of prognosis regarding pathologic stage after preoperative chemoradiotherapy in rectal cancer

AIM: To ascertain pathologic stage as a prognostic indicator for rectal cancer patients receiving preoperative chemoradiotherapy(PCRT).METHODS: Patients with mid- and low rectal carcinoma(magnetic resonance imaging- based clinical stage Ⅱ or Ⅲ) between 2000 and 2009 and treated with curative radical resection were identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence-free survival(RFS) was examined according to pathologic stage and addition of adjuvant treatment.RESULTS: Overall, 894 patients were identified. Of these, 500 patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No-PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6% for StageⅠ, 83.3% for Stage Ⅱ, and 72.9% for Stage Ⅲ. The 5-year RFS for the PCRT group was 95.2% for yp Stage 0, 91.7% for yp StageⅠ, 73.9% for yp Stage Ⅱ, and 50.7% for yp Stage Ⅲ.CONCLUSION: Pathologic stage can predict prognosis in PCRT patients. Five-year RFS is significantly lower among PCRT patients than No-PCRT patients in pathologic stage Ⅱ and Ⅲ. These results should be taken into account when considering adjuvant treatment for patients treated with PCRT.

Risk factors for local recurrence following neoadjuvant chemoradiotherapy for rectal cancers

Local recurrence(LR)has an adverse impact on rectal cancer treatment.Neoadjuvant chemoradiotherapy(nCRT)is increasingly administered to patients with progressive cancers to improve the prognosis.However,LR still remains a problem and its pattern can alter.Correspondingly,new risk factors have emerged in the context of nCRT in addition to the traditional risk factors in patients receiving non-neoadjuvant therapies.These risk factors are decisive when reviewing treatment options.This review aims to elucidate the distinctive risk factors related to LR of rectal cancers in patients receiving nCRT and to clarify their clinical significance.A search was conducted on PubMed to identify original studies investigating patients with rectal cancer receiving nCRT.Outcomes of interest,especially potential risk factors for LR in patients with nCRT,were then analyzed.The clinical importance of these risk factors is discussed.Remnant cancer cells,lymph-nodes and tumor response were found to be major risk factors.Remnant cancer cells decide the status of resection margins.Local excision following nCRT is promising in ypT0-1N0M0 cases.Dissection of lateral lymph nodes should be considered in advanced lowlying cancers.Although better tumor response resulted in a relatively lower recurrence rate,the evidence available is insufficient to justify a non-operative approach in clinical complete responders to nCRT.LR cannot be totally avoided by current multidisciplinary approaches.The related risk factors resulting from nCRT should be considered when making decisions regarding treatment selection.