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.

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.

Enhancing prognostic accuracy in predicting rectal neuroendocrine neoplasms

The recently published retrospective study introduces the GATIS score,a new predictive model for rectal neuroendocrine neoplasms.By analyzing data from a large Chinese multicenter cohort,the study shows that the GATIS score,incor-porating tumor grade,T stage,tumor size,age,and prognostic nutritional index,demonstrates superior predictive power for overall survival and progression-free survival compared to traditional World Health Organization grade and tumor,nodes and metastases staging systems.This editorial aims to discuss the impor-tance of the GATIS score,its potential impact on clinical practice,and the strengths and limitations of the study.Finally,it explores the significance,methodology,and clinical implications of these findings.

Evaluation of the GATIS score for predicting prognosis in rectal neuroendocrine neoplasms

The GATIS score,developed by Zeng et al,represents a significant advancement in predicting the prognosis of patients with rectal neuroendocrine neoplasms(RNENs).This study,which included 1408 patients from 17 major medical centres in China over 12 years,introduces a novel prognostic model based on the tumour grade,T stage,tumour size,age,and the prognostic nutritional index.Compared with traditional methods such as the World Health Organization classification and TNM staging systems,the GATIS score has superior predictive power for overall survival and progression-free survival.With a C-index of 0.915 in the training set and 0.812 in the external validation set,the GATIS score’s robustness and reliability are evident.The study’s use of a large,multi-centre cohort and rigorous validation processes underscore its significance.The GATIS score offers clinicians a powerful tool to accurately predict patient outcomes,guide treatment decisions,and improve follow-up strategies.This development represents a crucial step forwards in the management of R-NENs,addressing the complexity and variability of these tumours and setting a new benchmark for future research and clinical practice.

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.

Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Different oncological features of colorectal cancer codon-specific KRAS mutations:Not codon 13 but codon 12 have prognostic value

BACKGROUND Approximately 40%of colorectal cancer(CRC)cases are linked to Kirsten rat sarcoma viral oncogene homolog(KRAS)mutations.KRAS mutations are associated with poor CRC prognosis,especially KRAS codon 12 mutation,which is associated with metastasis and poorer survival.However,the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear.AIM To evaluate the clinicopathological characteristics and prognostic value of codonspecific KRAS mutations,especially in codon 13.METHODS This retrospective,single-center,observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019.Patients with KRAS mutation status confirmed by molecular pathology reports were included.The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed.Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model.RESULTS Among the 2203 patients,the incidence of KRAS codons 12,13,and 61 mutations was 27.7%,9.1%,and 1.3%,respectively.Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics,but only codon 12 was associated with pathological features,such as stage of primary tumor(T stage),lymph node involvement(N stage),vascular invasion,perineural invasion,tumor size,and microsatellite instability.KRAS codon 13 mutation showed no associations(77.2%vs 85.3%,P=0.159),whereas codon 12 was associated with a lower 5-year recurrence-free survival rate(78.9%vs 75.5%,P=0.025).In multivariable analysis,along with T and N stages and vascular and perineural invasion,only codon 12(hazard ratio:1.399;95%confidence interval:1.034-1.894;P=0.030)among KRAS mutations was an independent risk factor for recurrence.CONCLUSION This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.

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.

External validation of the Moroccan Arabic version of the European Organization for Research and Treatment of Cancer colorectal(CR29)module:Monocentric study

BACKGROUND Quality of life(QoL)outcomes are a focal endpoint of cancer treatment strategies.AIM To externally validate the Moroccan Arabic version of the European Organization for Research and Treatment of Cancer(EORTC)QoL Questionnaire(QLQ)for colorectal cancer(CRC)patients(CR29).METHODS Both Moroccan Arabic modules of QLQ-CR29 and QLQ-C30 were administered to Moroccan CRC.Psychometric properties were retested by measuring Cronbach’s alpha coefficient for reliability and Intraclass correlation coefficient(ICC)to examine test-retest reproducibility.The multitrait-scaling analysis was performed to demonstrate the validity of the instrument and known-groups comparison was used to test the score’s ability to discriminate between different groups of patients.RESULTS In total,221 patients were included in our study and 34 patients completed the questionnaire twice.The Urinary Frequency scale and Stool Frequency scale had good internal consistency with alpha Cronbach coefficients of 0.79 and 0.83 respectively,while the same coefficients were moderately lower for the Blood and Mucus in Stool scale(0.61)and the Body Image scale(0.67).The ICCs ranged from 0.88 to 1 indicating good to excellent reproducibility.In multitrait scaling analyses,the criterion for item convergent and divergent validity was satisfactory.The known-group comparison showed statistically significant differences between patients according to age,gender,stoma status,tumor location,and radiotherapy.CONCLUSION The Moroccan Arabic version of the EORTC QLQ-CR29 is a valid and reliable tool that can be used safely for research and clinical purposes in Moroccan CRC patients.

Racial differences in the anatomical distribution of colorectal cancer:a study of differences between American and Chinese patients

AIM: To compare the racial differences of anatomical distribution of colorectal cancer (CRC) and determine the association of age, gender and time with anatomical distribution between patients from America (white) and China (oriental).METHODS: Data was collected from 690 consecutive patients in Cleveland Clinic Florida, U.S.A. and 870consecutive patients in Nan Fang Hospital affiliated to the First Military Medical University, China over the past 11years from 1990 to 2000. All patients had colorectal adenocarcinoma diagnosed by histology and underwent surgery.RESULTS: The anatomical subsite distribution of tumor,age and gender were significantly different between white and oriental patients. Lesions in the proximal colon (P＜0.001) were found in 36.3 % of white vs 26.0 % of oriental patients and cancers located in the distal colon and rectum in 63.7 % of white and 74 % of oriental patients (P＜0.001). There was a trend towards the redistribution from distal colon and rectum to proximal colon in white males over time, especially in older patients (＞80 years).No significant change of anatomical distribution occurred in white women and Oriental patients. The mean age at diagnosis was 69.0 years in white patients and 48.3 years in Oriental patients (P＜0.001).CONCLUSION: This is the first study comparing the anatomical distribution of colorectal cancers in whites and Chinese patients. White Americans have a higher risk of proximal CRC and this risk increased with time. The proportion of white males with CRC also increased with time.Chinese patients were more likely to have distal CRC and developed the disease at a significantly earlier age than white patients. These findings have enhanced our understanding of the disease process of colorectal cancer in these two races.

Reduction of the incidence and mortality of rectal cancer bypolypectomy:a prospective cohort study in Haining County

AIM: To reduce the incidence and mortality of rectal cancer and address the hypothesis that colorectal cancer often arise from precursor lesion(s), either adenomas or non-adenomatous polyps, by conducting a population-based mass screening for colorectal cancer in Haining County, Zhejiang, PRC. METHODS: From 1977 to 1980, physicians screened the population of Haining County using 15 cm rigid endoscopy. Of over 240000 participants, 4076 of them were diagnosed with precursor lesions, either adenomas or non-adenomatous polyps, which were then removed surgically. All individuals with precursor lesions were followed up and reexamined by endoscopy every two to five years up to 1998. RESULTS: After the initial screening, 953 metachronous adenomas and 417 non-adenomatous polyps were detected and removed from the members of this cohort. Further, 27 cases of colorectal cancer were detected and treated. Log-rank tests showed that the survival time among those cancer patients who under went mass screening increased significantly compared to that of other colorectal cancer patients (P【0.0001). According to the population-based cancer registry in Haining County, age-adjusted incidence and mortality of rectal cancer decreased by 41% and 29% from 1977-1981 to 1992-1996, respectively. Observed cumulative 20-year rectal cancer incidence was 31% lower than the expected in the screened group; the mortality due to rectal cancer was 18% lower than the expected in the screened group. CONCLUSION:Mass screening for rectal cancer and precursor lesions with protocoscopy in the general population and periodical following-up with routine endoscopy for high-risk patients may decrease both the incidence and mortality of rectal cancer.

Comparison of hydrocolonic sonograpy accuracy in preoperative staging between colon and rectal cancer

AIM:To compare the accuracy of hydrocolonic sonography (HUS) in determining the depth of invasion (T stage) in colon and rectal cancer. METHODS:A total of 1000-2000 mL of saline was instilled per rectum using a system for barium enemas,and then ultrasonography was conducted by a SSA-270A (Toshiba Co,Japan) sonolayer unit with a 3.75 MHz for 17 patients with colon cancer and 13 patients with rectal cancer before operation.After operation,T stage in HUS was compared with postoperative histological findings. RESULTS:Overall,the accuracy of T stage was 70%.It was 88% in colon cancer and 46% in rectal cancer.In evaluating nodal state,the accuracy of HUS was low in both colon (71%) and rectal cancers (46%) compared with conventional CT or MRI.The overall accuracy of N staging was 60%. CONCLUSION:HUS is valuable to evaluate the depth of invasion in colon cancer,but is less valuable in rectal cancer.Because HUS is low-cost,noninvasive,and readily available at any place,this technique seems to be useful to determine the preoperative staging in colon cancer,but not in rectal cancer.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer

BACKGROUND Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer.Neoadjuvant chemoradiotherapy(NCRT)can effectively reduce the postoperative recurrence rate;thus,NCRT with total mesorectal excision(TME)is the most widely accepted standard of care for rectal cancer.The addition of lateral lymph node dissection(LLND)after NCRT remains a controversial topic.AIM To investigate the surgical outcomes of TME plus LLND,and the possible risk factors for lateral lymph node metastasis after NCRT.METHODS This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018.In the NCRT group,TME plus LLND was performed in patients with short axis(SA)of the lateral lymph node greater than 5 mm.In the non-NCRT group,TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm.Data regarding patient demographics,clinical workup,surgical procedure,complications,and outcomes were collected.Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients.RESULTS LLN metastasis was pathologically confirmed in 35 patients(39.3%):26(41.3%)in the NCRT group and 9(34.6%)in the non-NCRT group.The most common site of metastasis was around the obturator nerve(21/35)followed by the internal iliac artery region(12/35).In the NCRT patients,46%of patients with SA of LLN greater than 7 mm were positive.The postoperative 30-d mortality rate was 0%.Two(2.2%)patients suffered from lateral local recurrence in the 2-year follow up.Multivariate analysis showed that cT4 stage(odds ratio[OR]=5.124,95%confidence interval[CI]:1.419-18.508;P=0.013),poor differentiation type(OR=4.014,95%CI:1.038-15.520;P=0.044),and SA≥7 mm(OR=7.539,95%CI:1.487-38.214;P=0.015)were statistically significant risk factors associated with LLN metastasis.CONCLUSION NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter,poorer histological differentiation,or advanced T stage.Selective LLND for NCRT patients can have a favorable oncological outcome.

Robotic surgery for rectal cancer: Current immediate clinical and oncological outcomes

Laparoscopic rectal surgery continues to be a challenging operation associated to a steep learning curve. Robotic surgical systems have dramatically changed minimally invasive surgery. Three-dimensional, magnified and stable view, articulated instruments, and reduction of physiologic tremors leading to superior dexterity and ergonomics. Therefore, robotic platforms could potentially address limitations of laparoscopic rectal surgery. It was aimed at reviewing current literature on short-term clinical and oncological(pathological) outcomes after robotic rectal cancer surgery in comparison with laparoscopic surgery. A systematic review was performed for the period 2002 to 2014. A total of 1776 patients with rectal cancer underwent minimally invasive robotic treatment in 32 studies. After robotic and laparoscopic approach to oncologic rectal surgery, respectively, mean operating time varied from 192-385 min, and from 158-297 min; mean estimated blood loss was between 33 and 283 mL, and between 127 and 300 mL; mean length of stay varied from 4-10 d; and from 6-15 d. Conversion after robotic rectal surgery varied from 0% to 9.4%, and from 0 to 22% after laparoscopy. There was no difference between robotic(0%-41.3%) and laparoscopic(5.5%-29.3%) surgery regarding morbidity and anastomotic complications(respectively, 0%-13.5%, and 0%-11.1%). Regarding immediate oncologic outcomes, respectively among robotic and laparoscopic cases, positive circumferential margins varied from 0% to 7.5%, and from 0% to 8.8%; the mean number of retrieved lymph nodes was between 10 and 20, and between 11 and 21; and the mean distal resection margin was from 0.8 to 4.7 cm, and from 1.9 to 4.5 cm. Robotic rectal cancer surgery is being undertaken by experienced surgeons. However, the quality of the assembled evidence does not support definite conclusions about most studies variables. Robotic rectal cancer surgery is associated to increased costs and operating time. It also seems to be associated to reduced conversion rates. Other short-term outcomes are comparable to conventional laparoscopy techniques, if not better. Ultimately, pathological data evaluation suggests that oncologic safety may be preserved after robotic total mesorectal excision. However, further studies are required to evaluate oncologic safety and functional results.

Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer

AIM： To investigate the effect of three-dimensional conformal radiotherapy （3-DCRT） in combination with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer. METHODS： Forty-eight patients with unresectable recurrent rectal cancer were randomized and treated by 3-DCRT or 3-DCRT combined with FOLFOX4 chemotherapy between September 2001 and October 2003. For the patients without prior radiation history, the initial radiation was given to the whole pelvis by traditional methods with tumor dose of 40 Gy, followed by 3-DCRT for the recurrent lesions to the median total cumulative tumor dose of 60 Gy （range 56-66 Gy）; for the post-radiation recurrent patients, 3-DCRT was directly given for the recurrent lesions to the median tumor dose of 40 Gy （36-46 Gy）. For patients in the study group, two cycles chemotherapy with FOLFOX4 regimen were given concurrently with radiotherapy, with the first cycle given simultaneously with the initiation of radiation and the second cycle given in the fifth week for patients receiving conventional pelvis radiation or given in the last week of 3-DCRT for patients receiving 3-DCRT directly. Another 2-4 cycles （average 3.6 cycles） sequential FOLFOX4 regimen chemotherapy were given to the patients in the study group, beginning at 2-3 wk after chemoradiation. The outcomes of symptoms relieve, tumor response, survival and toxicity were recorded and compared between the study group and the control group. RESULTS： For the study group and the control group, the pain-alleviation rates were 95.2% and 91.3%（P〉 0.05）; the overall response rates were 56.5% and 40.0% （P〉0.05）; the 1-year and 2-year survival rates were 86.9%, 50.2% and 80.0%, 23.9%, with median survival time of 25 mo and 16 mo （P〈 0.05）; the 2-year distant metastasis rates were 39.1% and 56.0% （P= 0.054）, respectively. The side effects, except peripheral neuropathy which was relatively severer in the study group, were similar in the the two groups and well tolerated. CONCLUSION： Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer is a feasible and effective therapeutic approach, and can reduce distant metastasis rate and improve the survival rate.

Surgical resection of rectal adenoma:A rapid review

Transanal excision （TE）, endoscopic transanal resection （ETAR） and transanal endoscopic microsurgery （TEN） can be used to remove adenomatous polyps. However, their use is limited by the size or location of the tumor. TE is limited to the lower rectum, TEN offers better access to lesions in the middle and upper rectum, and ETAR is used less frequently than it deserves for resection of rectal lesions.

Low ligation has a lower anastomotic leakage rate after rectal cancer surgery

BACKGROUND For laparoscopic rectal cancer surgery,the inferior mesenteric artery(IMA)can be ligated at its origin from the aorta[high ligation(HL)]or distally to the origin of the left colic artery[low ligation(LL)].Whether different ligation levels are related to different postoperative complications,operation time,and lymph node yield remains controversial.Therefore,we designed this study to determine the effects of different ligation levels in rectal cancer surgery.AIM To investigate the operative results following HL and LL of the IMA in rectal cancer patients.METHODS From January 2017 to July 2019,this retrospective cohort study collected information from 462 consecutive rectal cancer patients.According to the ligation level,235 patients were assigned to the HL group while 227 patients were assigned to the LL group.Data regarding the clinical characteristics,surgical characteristics and complications,pathological outcomes and postoperative recovery were obtained and compared between the two groups.A multivariate logistic regression analysis was performed to evaluate the possible risk factors for anastomotic leakage(AL).RESULTS Compared to the HL group,the LL group had a significantly lower AL rate,with 6(2.8%)cases in the LL group and 24(11.0%)cases in the HL group(P=0.001).The HL group also had a higher diverting stoma rate(16.5%vs 7.5%,P=0.003).A multivariate logistic regression analysis was subsequently performed to adjust for the confounding factors and confirmed that HL(OR=3.599;95%CI:1.374-9.425;P=0.009),tumor located below the peritoneal reflection(OR=2.751;95%CI:0.772-3.985;P=0.031)and age(≥65 years)(OR=2.494;95%CI:1.080-5.760;P=0.032)were risk factors for AL.There were no differences in terms of patient demographics,pathological outcomes,lymph nodes harvested,blood loss,hospital stay and urinary function(P>0.05).CONCLUSION In rectal cancer surgery,LL should be the preferred method,as it has a lower AL and diverting stoma rate.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is(limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Peripheral and mesenteric serum levels of CEA and cytokeratins,staging and histopathological variables in colorectal adenocarcinoma

AIM： To evaluate the differences that exist bet- ween peripheral and mesenteric serum levels of carcinoembryonic antigen （CEA） and cytokeratins in patients with colorectal adenocarcinoma. METHODS： One hundred and thirty-eight patients with colorectal adenocarcinoma who underwent surgery at Hospital Sao Paulo （Discipline of Surgical Gastroenterology of UNIFESP-EPM） between December 1993 and March 2000 were retrospectively analyzed. Differences between CEA and cytokeratin （TPA-M） levels in peripheral blood （P） and in mesenteric blood （M） were studied. Associations were investigated between peripheral and mesenteric levels and the staging and histopathological variables （degree of cell differentiation, macroscopic appearance, tumor dimensions and presence of lymphatic and venous invasion）. RESULTS： Differences were observed in the numerical values of the marker levels： CEA （M） （39.10 mg/1 ± 121.19 mg/L） vs CEA （P） （38.5 mg/L ± 122.55 mg/L）, P 〈 0.05; TPA-M （M） （325.06 U/L ±527.29 U/L） vs TPA-M （P） （279.48 U/L ±455.81 U/L）, P 〈 0.01. The mesenteric CEA levels were higher in more advanced tumors （P 〈 0.01）, in vegetating lesions （34.44 mg/L ± 93.07 mg/L） （P 〈 0.01） and with venous invasion （48.41 mg/L ± 129.86 mg/L） （P 〈 0.05）. Peripheral CEA was higher with more advanced staging （P 〈 0.01）and in lesions with venous invasion （53.23 mg/L ± 258.57 mg/L） （P 〈 0.05）. The patients demonstrated increased mesenteric and peripheral TPA-M levels with more advanced tumors （P 〈 0.01 and P 〈 0.01） and in non-ulcerated lesions [530.45 U/L =1= 997.46 U/L （P 〈 0.05） and 457.95 U/L ± 811.36 U/L （P 〈 0.01）]. CONCLUSION： The mesenteric levels of the tumor markers CEA and cytokeratins were higher than the peripheral levels in these colorectal adenocarcinoma patients, Higher levels of these biologic tumor markers are associated with an advanced state of cancerous dissemination

Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.