Local excision for middle-low rectal cancer after neoadjuvant chemoradiation:A retrospective study from a single tertiary center

BACKGROUND Rectal cancer has become one of the leading malignancies threatening people’s health.For locally advanced rectal cancer(LARC),the comprehensive strategy combining neoadjuvant chemoradiotherapy(NCRT),total mesorectal excision(TME),and adjuvant chemotherapy has emerged as a standard treatment regimen,leading to favorable local control and long-term survival.However,in recent years,an increasing attention has been paid on the exploration of organ preservation strategies,aiming to enhance quality of life while maintaining optimal oncological treatment outcomes.Local excision(LE),compared with low anterior resection(LAR)or abdominal-perineal resection(APR)was introduced dating back to 1970’s.LE has historically been linked to a heightened risk of recurrence compared to TME,potentially due to occult lymph node metastasis and intraluminal recurrence.Recent evidence has demonstrated that LE might be an alternative approach,instead of LAR or APR,in cases with favorable tumor regression after NCRT with potentially better quality of life.Therefore,a retrospective analysis of clinicopathological data from mid-low LARC patients who underwent LE after NCRT was conducted,aiming to evaluate the treatment's efficacy,safety,and oncologic prognosis.AIM To explore the safety,efficacy,and long-term prognosis of LE in patients with mid-low rectal cancer who had a good response to NCRT.METHODS Patients with LE between 2012 to 2021 were retrospectively collected from the rectal cancer database from Gastro-intestinal Ward III in Peking University Cancer Hospital.The clinicopathological features,postoperative complications,and long-term prognosis of these patients were analyzed.The Kaplan-Meier method was used to create cancer-specific survival curve,and the log-rank test was used to compare the differences regarding outcomes.RESULTS A total of 33 patients were included in this study.The median interval between NCRT and surgery was 25.4(range:8.7-164.4)weeks.The median operation time was 57(20.0-137.0)minutes.The initial clinical T staging(cT):9(27.3%)patients were cT2,19(57.6%)patients were cT3,and 5(15.2%)patients were cT4;The initial N staging(cN):8 patients(24.2%)were cN negative,25 patients(75.8%)were cN positive;The initial M stage(cM):2 patients(6.1%)had distant metastasis(ycM1),31(93.9%)patients had no distant metastasis(cM0).The pathological results:18(54.5%)patients were pathological T0 stage(ypT0),6(18.2%)patients were ypT1,7(21.2%)patients were ypT2,and 2(6.1%)patients were ypT3.For 9 cT2 patients,5(5/9,55.6%)had a postoperative pathological result of ypT0.For 19 cT3 patients,11(57.9%)patients were ypT0,and 2(40%)were ypT0 in 5 cT4 patients.The most common complication was chronic perineal pain(71.4%,5/7),followed by bleeding(43%,3/7),stenosis(14.3%,1/7),and fecal incontinence(14.3%,1/7).The median follow-up time was 42.0(4.0-93.5)months.For 31 patients with cM0,the 5-year disease-free survival(DFS)rate,5-year local recurrence-free survival(LRFS)rate,and 5-year overall survival(OS)rate were 88.4%,96.7%,and 92.9%,respectively.There were significant differences between the ycT groups concerning either DFS(P=0.042)or OS(P=0.002)in the Kaplan-Meier analysis.The LRFS curve of ycT≤T1 patients was better than that of ycT≥T2 patients,and the P value was very close to 0.05(P=0.070).The DFS curve of patients with ypT≤T1 was better than that of patients with ypT≥T2,but the P value was not statistically significant(P=0.560).There was a significant difference between the ypT groups concerning OS(P=0.014)in the Kaplan-Meier analysis.The LRFS curve of ypT≤T1 patients was better than that of ypT≥T2 patients,and the P value was very close to 0.05(P=0.070).Two patients with initial cM1 were alive at the last follow-up.CONCLUSION LE for rectal cancer with significant tumor regression after NCRT can obtain better safety,efficiency,and oncological outcome.Minimally invasive or nonsurgical treatment with patient participation in decision-making can be performed for highly selected patients.Further investigation from multiple centers will bring better understanding of potential advantages regarding local resection.

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies

BACKGROUND Programmed death protein(PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient(dMMR)/microsatellite instability-high(MSI-H)gastrointestinal malignancies such gastric and colorectal cancer.However,the data on preoperative immunotherapy are limited.AIM To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.METHODS In this retrospective study,we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies.All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively.PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.RESULTS Three patients with locally advanced gastric cancer achieved pathological complete response(pCR).Three patients with locally advanced duodenal carcinoma achieved clinical complete response(cCR),followed by watch and wait.Eight of 16 patients with locally advanced colon cancer achieved pCR.All four patients with liver metastasis from colon cancer reached CR,including three with pCR and one with cCR.pCR was achieved in two of five patients with nonliver metastatic colorectal cancer.CR was achieved in four of five patients with low rectal cancer,including three with cCR and one with pCR.cCR was achieved in seven of 36 cases,among which,six were selected for watch and wait strategy.No cCR was observed in gastric or colon cancer.CONCLUSION Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR,especially in patients with duodenal or low rectal cancer,and can achieve high organ function protection.

Anesthetic management of a patient with preoperative R-on-T phenomenon undergoing laparoscopic-assisted sigmoid colon resection:A case report

BACKGROUND The R-on-T phenomenon is a malignant arrhythmia associated with potentially catastrophic consequences.It may initiate ventricular tachycardia or ventricular fibrillation,which can result in syncope or sudden cardiac death.This manifestation poses a great challenge for anesthesiologists.However,it is rarely encountered in the perioperative setting.CASE SUMMARY We herein present a case in which the R-on-T phenomenon was incidentally revealed by 24-h Holter monitoring in a patient diagnosed with sigmoid colon cancer.Careful evaluation and treatment with mexiletine were carried out preoperatively under consultation with a cardiovascular specialist,and surgery was uneventfully performed under general anesthesia after thorough preparation.CONCLUSION Physicians should be vigilant about this infrequent but potentially fatal arrhythmia.Our experience suggests that the anesthetic process can be greatly optimized with careful preparation.

直接前入路与后外侧入路初次全髋关节置换术患者的临床疗效比较

目的研究经直接前入路和后外侧入路初次全髋关节置换术(THA)患者的临床疗效。方法选取2016年1月—2019年7月于安徽医科大学第二附属医院骨科行初次单侧全髋关节置换术285例患者的临床资料。其中采用直接前入路(DAA)患者100例作为DAA组,后外侧入路(PLA)患者185例作为PLA组。观察并分析两组患者失血量、手术时间等围手术期指标,VAS评分、Harris评分及髋关节活动(屈曲、后伸、内收、外展、内旋、外旋)等功能评价指标。结果DAA组失血总量、隐性失血量、隐性失血量占比小于PLA组(P<0.05),手术时间、直腿抬高时间短于PLA组(P<0.05)。两组患者不同时间点的Harris评分、VAS评分、ROM指标比较,经重复测量设计的方差分析,结果:(1)不同时间点Harris评分、VAS评分、ROM指标有差异(P<0.05);(2)两组患者Harris评分、VAS评分有差异(P<0.05),ROM指标无差异(P>0.05);(3)两组患者Harris评分、VAS评分变化趋势有差异(P<0.05),ROM指标变化趋势比较无差异(P>0.05)。结论采用DAA行初次单侧THA可有效降低围手术期的失血量、缩短手术时间、减少术后疼痛,有利于早期功能恢复。

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect

Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been completely deciphered.This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF.The methods included collection and screening of chemical components,prediction of depression-associated targets of the active components,gene enrichment,and network construction and analysis.Quercetin and 4 other active components were found to exert an tidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand・wceptor interaction pathways.DRD2,HTR1 A,and SLC6A4 were identified as important targets of the studied bioactive components of AF.This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

Tumor regression grades:Potential outcome predictor of locally advanced rectal adenocarcinoma after preoperative radiotherapy

AIM:To analyze tumor regression grade(TRG)for prognosis of locally advanced rectal adenocarcinoma(LARA)treated with preoperative radiotherapy.METHODS:One hundred and ninety patients with clinical stageⅡ/ⅢLARA were studied.All patients underwent radical surgery(between 2004 and 2010)after 30-Gy/10-fraction preoperative radiotherapy(preRT).All 190 patients received a short course of preRT and were reassessed for disease recurrence and survival;the slides of surgical specimens were reviewed and classified according to Mandard TRG.We compared patients with good response(Mandard TRG1 or TRG2)vs patients with bad/poor response(Mandard TRG3-5).Outcomes evaluated were 5-year overall survival(OS),5-year disease-free survival(DFS),and local,distant and mixed recurrence.Fisher’s exact test orχ2 test,logrank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes.RESULTS:One hundred and sixty-six of 190 patients(87.4%)were identified as Mandard bad responders(TRG3-5).High Mandard grade was correlated with tumor height(41.7%<6 cm vs 58.3%≥6 cm,P=0.050),yp T stage(75%yp T0-2 vs 25%yp T3-4,P=0.000),and yp N stage(75%yp N0 vs 25%yp N1,P=0.031).In univariate survival analysis,Mandard grade bad responders had significantly worse OS and DFSthan good responders(TRG1/2)(OS,83.1%vs 96.4%,P=0.000;DFS,72.3%vs 92.0%,P=0.002).In multivariate survival analysis,Mandard bad responders had significantly worse DFS than Mandard good responders(DFS 3.8 years(95%CI:1.2-12.2 years,P=0.026).CONCLUSION:Mandard grade good responders had a favorable prognosis.TRG may be a potential predictor for DFS in LARA after pre-RT.

Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas

BACKGROUND Human epidermal growth factor receptor 2(HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas(CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.AIM To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC.METHODS About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining(IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization(FISH) to assess HER2 gene amplification. Follow-up information was availablefor 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.RESULTS HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31(2.6%), 105(8.8%), 475(39.7%), and 584(48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+(82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+(11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+(0/10). HER2 gene amplification was seen in 36/1191 tumors(3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+and 2+, the mean percentage of tumor cells with positive IHC staining was 90%(median 100%, range 40%-100%) and 67%(median 75%, range 5%-95%),respectively(P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining(n = 12, mean 93%, median 95%, range 90%-95%) than those without(n =90, mean 70%, median 50%, range 5%-95%)(P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage(P = 0.028 and0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival(OS)or disease-specific survival for the overall group of 1058 patients. However,further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger(n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without(mean: 47.9 mo vs 65.1 mo, P =0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores(2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores(0, 1+)(47.2 mo vs64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores(47.1 mo vs 64.8 mo, P = 0.031).CONCLUSION HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

Trans-anal minimally invasive surgery for rectal neoplasia:Experience from single tertiary institution in China

AIM To evaluate the feasibility and safety of trans-anal minimally invasive surgery(TAMIS) from single institute in China. METHODS A retrospective review was conducted for patients with rectal neoplasia, who underwent TAMIS using single incision laparoscopic surgery-Port from January 2013 till January 2016 by a group of colorectal surgeons from Gastrointestinal Center Unit Ⅲ, Peking University Cancer Hospital. Patients' demographic data, surgical related information, post-operational pathology, as well as perioperative follow-up were all collected. RESULTS Twenty-five patients with rectal neoplasia were identified consequently. Complete full-thickness excision was achieved in all cases without conversion. 22(88%) cases had rectal malignancies [6 were adenocarcinomas and 16 were neuroendocrine tumors(NET)], while 3 patients had adenomas. Mean surgical duration was 61.3 min, and mean post-operative stay were 2.7 d. Post-operational examination demonstrated 5 cases had positive resection margin: 2 adenocarcinoma cases and 1 NET case with positive lateral margin, and the other 2 NET cases with positive basal margin. The curve of operation time for TAMIS cases suggested a minimum of 10 cases for a laparoscopic surgeon proficient withthis technique. CONCLUSION TAMIS was demonstrated to be reproducible and safe,with a relatively short learning process for laparoscopic surgeons in selected cases for rectal neoplasia. Longterm oncological outcome needs to be determined by further investigation.

Fat clearance and conventional fixation identified ypN0 rectal cancers following intermediate neoadjuvant radiotherapy have similar long-term outcomes

BACKGROUND As a prognostic factor for colorectal cancer,lymph node(LN)status,particularly the number of LN harvested,has been demonstrated to be essential in the evaluation of quality control in terms of surgical specimen.Neoadjuvant chemoradiation,however,decreases the LN harvest.Therefore,certain approaches(such as fat clearance or methylene blue)has drawn significant attention in order to raise LN yield.AIM To compare the long-term oncologic outcome of ypN0 rectal cancer identified using fat clearance(FC)or conventional fixation(CF)following 30 Gy in 10 fractions(30 Gy/10f)of neoadjuvant radiotherapy(nRT).METHODS Three hundred and eighty-two patients with resectable and locally advanced rectal cancer were treated by 30 Gy/10f intermediate nRT(biologically equivalent dose of 36 Gy)plus total mesorectal excision.Two specimen fixation methods(FC or CF)were non-randomly used.The ypN0 status was identified in 124 and 101 patients in the FL and CF groups,respectively.Primary endpoints were local recurrence-free survival(LRFS)and cancer-specific survival(CSS).RESULTS The median follow-up of patients was 5.1 years.The median numbers of retrieved LNs in the FC and CF groups were 19.5(range,4-47)and 12(range,0-44),respectively,with a significant difference(P=0.000).The percentages of patients with 12 or more retrieved nodes were 82.3%and 50.5%(101/159)in the FC and CF groups,respectively,with a significant difference(P=0.000).The LRFS at 5 years were 95.7%and 94.6%in the FC and CF groups,respectively,without statistical difference(P=0.819).The CSS at 5 years were 92.0%and 87.2%in the FC and CF groups,respectively,without statistical difference(P=0.482).CONCLUSION For patients with ypN0 rectal cancer who underwent 30 Gy/10f preoperative radiotherapy,the increased retrieval of LNs using fat clearance is not associated with survival benefit.This time-consuming fixation method has a low efficacy as a routine practice.

Long-term follow-up of HER2 overexpression in patients with rectal cancer after preoperative radiotherapy:A prospective cohort study

BACKGROUND The role of HER2 overexpression in rectal cancer is controversial.AIM To assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.METHODS Data from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected.A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy,followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients’HER2 expression status.Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed.Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status,and the differences between groups were verified using the log-rank test.RESULTS A total of 151 patients were enrolled in this study.A total of 27(17.9%)patients were ultimately confirmed to be HER2-positive.The follow-up duration ranged from 9 mo to 210 mo,with a median of 134 mo.Distant metastasis and local recurrence occurred in 60(39.7%)and 24(15.9%)patients,respectively.HER2 positivity was significantly associated with the pre-treatment lymph node stage(pre-N)(P=0.040),while there were no differences between HER2 status and age,sex,preoperative CEA levels(pre-CEA),T stage,and lympho-vascular invasion.In terms of prognosis,HER2 overexpression was correlated with distant meta stasis(P=0.002)rather than local recurrence(P>0.05).The multivariate analysis demonstrated that elevated pre-CEA[P=0.002,odds ratio(OR)=3.277,97.5%confidence interval(CI):1.543-7.163],post N(+)(P=0.022,OR=2.437,97.5%CI:1.143-5.308)and HER2(+)(P=0.003,OR=4.222,97.5%CI:1.667-11.409)were risk factors for distant metastasis.The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival(DFS)[hazard ratio:1.69(95%CI:0.91-3.14);P=0.048]and overall survival(OS)[1.95(1.05-3.63);P=0.0077].CONCLUSION HER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis,which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer:a single-center,single-arm,prospective Phase II trial(PKUCH-R02)

Background:Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk,locally advanced rectal cancer.However,the benefit of more intensive total neoadjuvant treatment(TNT)is unknown.This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer.Methods:This was a single-center,single-arm,prospective Phase II trial in Peking University Cancer Hospital(Beijing,China).Patients received three cycles of induction oxaliplatin and capecitabine(CapeOX)followed by chemoradiotherapy and two cycles of consolidation CapeOX.The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate,completion of TNT,and pathological downstaging rate.Results:Between August 2017 and August 2018,68 rectal cancer patients with at least one high risk factor(cT3c/3d/T4a/T4b,cN2,mesorectal fascia involvement,or extramural venous invasion involvement)were enrolled.The overall compliance of receiving the entire treatment was 88.2%(60/68).All 68 patients received induction chemotherapy,65 received chemoradiotherapy,and 61 received consolidation chemotherapy.The Grade 3–4 adverse event rate was 30.8%(21/68).Nine patients achieved clinical complete response and then watch and wait.Five patients(7.4%)developed distant metastasis during TNT and received palliative chemotherapy.Fifty patients underwent surgical resection.The complete response rate was 27.9%.After a median follow-up of 49.2 months,the overall 3-year disease-free survival rate was 69.7%.Conclusions:For patients with high-risk rectal cancer,this TNT regimen can achieve favorable survival and complete response rates but with high toxicity.However,it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.