Fascia- vs vessel-oriented lateral lymph node dissection for rectal cancer: Short-term outcomes and prognosis in a single-center experience

BACKGROUND For the management of lateral lymph node(LLN)metastasis in patients with rectal cancer,selective LLN dissection(LLND)is gradually being accepted by Chinese scholars.Theoretically,fascia-oriented LLND allows radical tumor resection and protects of organ function.However,there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND.Through a preliminary study with a small sample size,we found that fasciaoriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs.In this study,we increased the sample size and refined the postoperative functional outcomes.AIM To compare the effects of fascia-and vessel-oriented LLND regarding short-term outcomes and prognosis.METHODS We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021.The short-term outcomes included perioperative outcomes and postoperative functional outcomes.The prognosis was measured based on overall survival(OS)and progression-free survival(PFS).RESULTS A total of 105 patients were included in the final analysis and were divided into fascia-and vesseloriented groups that included 41 and 64 patients,respectively.Regarding the short-term outcomes,the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group.There were no significant differences in the other short-term outcomes.The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group.In addition,there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups.In terms of prognosis,there was no significant difference in PFS or OS between the two groups.CONCLUSION It is safe and feasible to perform fascia-oriented LLND.Compared with vessel-oriented LLND,fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments

BACKGROUND It remains unclear whether laparoscopic multisegmental resection and ana-stomosis(LMRA)is safe and advantageous over traditional open multisegmental resection and anastomosis(OMRA)for treating synchronous colorectal cancer(SCRC)located in separate segments.AIM To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments.METHODS Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital,Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited.In accordance with the RESULTS LMRA patients showed markedly less intraoperative blood loss than OMRA patients(100 vs 200 mL,P=0.006).Compared to OMRA patients,LMRA patients exhibited markedly shorter postoperative first exhaust time(2 vs 3 d,P=0.001),postoperative first fluid intake time(3 vs 4 d,P=0.012),and postoperative hospital stay(9 vs 12 d,P=0.002).The incidence of total postoperative complications(Clavien-Dindo grade:≥II)was 2.9%and 17.1%(P=0.025)in the LMRA and OMRA groups,respectively,while the incidence of anastomotic leakage was 2.9%and 7.3%(P=0.558)in the LMRA and OMRA groups,respectively.Furthermore,the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group(45.2 vs 37.3,P=0.020).The 5-year overall survival(OS)and disease-free survival(DFS)rates in OMRA patients were 82.9%and 78.3%,respectively,while these rates in LMRA patients were 78.2%and 72.8%,respectively.Multivariate prognostic analysis revealed that N stage[OS:HR hazard ratio(HR)=10.161,P=0.026;DFS:HR=13.017,P=0.013],but not the surgical method(LMRA/OMRA)(OS:HR=0.834,P=0.749;DFS:HR=0.812,P=0.712),was the independent influencing factor in the OS and DFS of patients with SCRC.CONCLUSION LMRA is safe and feasible for patients with SCRC located in separate segments.Compared to OMRA,the LMRA approach has more advantages related to short-term efficacy.

Long-term outcomes and failure patterns after laparoscopic intersphincteric resection in ultralow rectal cancers

BACKGROUND Intersphincteric resection(ISR),the ultimate anus-preserving technique for ultralow rectal cancers,is an alternative to abdominoperineal resection(APR).The failure patterns and risk factors for local recurrence and distant metastasis remain controversial and require further investigation.AIM To investigate the long-term outcomes and failure patterns after laparoscopic ISR in ultralow rectal cancers.METHODS Patients who underwent laparoscopic ISR(LsISR)at Peking University First Hospital between January 2012 and December 2020 were retrospectively reviewed.Correlation analysis was performed using the Chi-square or Pearson's correlation test.Prognostic factors for overall survival(OS),local recurrence-free survival(LRFS),and distant metastasis-free survival(DMFS)were analyzed using Cox regression.RESULTS We enrolled 368 patients with a median follow-up of 42 mo.Local recurrence and distant metastasis occurred in 13(3.5%)and 42(11.4%)cases,respectively.The 3-year OS,LRFS,and DMFS rates were 91.3%,97.1%,and 90.1%,respectively Multivariate analyses revealed that LRFS was associated with positive lymph node status[hazard ratio(HR)=5.411,95%confidence interval(CI)=1.413-20.722,P=0.014]and poor differentiation(HR=3.739,95%CI:1.171-11.937,P=0.026),whereas the independent prognostic factors for DMFS were positive lymph node status(HR=2.445,95%CI:1.272-4.698,P=0.007)and(y)pT3 stage(HR=2.741,95%CI:1.225-6.137,P=0.014).CONCLUSION This study confirmed the oncological safety of LsISR for ultralow rectal cancer.Poor differentiation,(y)pT3 stage,and lymph node metastasis are independent risk factors for treatment failure after LsISR,and thus patients with these factors should be carefully managed with optimal neoadjuvant therapy,and for patients with a high risk of local recurrence(N+or poor differentiation),extended radical resection(such as APR instead of ISR)may be more effective.

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.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients

BACKGROUND Epidemiologically,in China,locally advanced rectal cancer is a more common form of rectal cancer.Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival(DFS)and pathologic response after surgery.At present,this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers,but the optimal time for surgery after neoadjuvant therapy is still controversial.AIM To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer.METHODS A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study.The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery:139(60.2%)patients were in group A(≤9 wk),and 92(39.2%)patients were in group B(>9 wk).DFS and pathologic response were analyzed as the primary endpoints.The secondary endpoints were postoperative complications and sphincter preservation.RESULTS For the 231 patients included,surgery was performed at≤9 wk in 139(60.2%)patients and at>9 wk in 92(39.8%).The patients’clinical characteristics,surgical results,and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis.The overall pathologic complete response(pCR)rate was 27.2%(n=25)in the longer time interval group(>9 wk)and 10.8%(n=15)in the shorter time interval group(≤9 wk,P=0.001).The postoperative complications did not differ between the groups(group A,5%vs group B,5.4%;P=0.894).Surgical procedures for sphincter preservation were performed in 113(48.9%)patients,which were not significantly different between the groups(group A,52.5%vs group B,43.5%;P=0.179).The pCR rate was an independent factor affected by time interval(P=0.009;odds ratio[OR]=2.668;95%CI:1.276-5.578).Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval(>9 wk)was a significant independent prognostic factor for DFS(P=0.032;OR=2.295;95%CI:1.074-4.905),but the time interval was not an independent prognostic factor for overall survival(P>0.05).CONCLUSION A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

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.

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy

BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors

BACKGROUND Intraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL. AIM To investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms. METHODS This retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis. RESULTS The univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386;95%CI: 1.808-16.042;P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer. CONCLUSION Intraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals

BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.

Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy

BACKGROUND Conventional clinical guidelines recommend that at least 12 lymph nodes shouldbe removed during radical rectal cancer surgery to achieve accurate staging.Thecurrent application of neoadjuvant therapy has changed the number of lymphnode dissection.AIM To investigate factors affecting the number of lymph nodes dissected afterneoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluatethe relationship of the total number of retrieved lymph nodes(TLN)with diseasefreesurvival(DFS)and overall survival(OS).METHODS A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 wereincluded in this study.According to the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor-node-metastasis(TNM)classification system and the NCCN guidelines for rectal cancer,thepatients were divided into two groups:group A(TLN≥12,n=177)and group B(TLN<12,n=54).Factors influencing lymph node retrieval were analyzed byunivariate and binary logistic regression analysis.DFS and OS were evaluated byKaplan-Meier curves and Cox regression models.RESULTS The median number of lymph nodes dissected was 18(range,12-45)in group A and 8(range,2-11)in group B.The lymph node ratio(number of positive lymphnodes/total number of lymph nodes)(P=0.039)and the interval betweenneoadjuvant therapy and radical surgery(P=0.002)were independent factors ofthe TLN.However,TLN was not associated with sex,age,ASA score,clinical T orN stage,pathological T stage,tumor response grade(Dworak),downstaging,pathological complete response,radiotherapy dose,preoperative concurrentchemotherapy regimen,tumor distance from anal verge,multivisceral resection,preoperative carcinoembryonic antigen level,perineural invasion,intravasculartumor embolus or degree of differentiation.The pathological T stage(P<0.001)and TLN(P<0.001)were independent factors of DFS,and pathological T stage(P=0.011)and perineural invasion(P=0.002)were independent factors of OS.Inaddition,the risk of distant recurrence was greater for TLN<12(P=0.009).CONCLUSION A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectalcancer under indications may cause increased number of lymph nodes harvested.Tumor shrinkage and more extensive lymph node retrieval may lead to a morefavorable prognosis.

Classification and genetic counselling for a novel splicing mutation of the MLH1 intron associated with Lynch syndrome in colorectal cancer

Background:Lynch-syndrome-associated cancer is caused by germline pathogenic mutations in mismatch repair genes.The major challenge to Lynch-syndrome screening is the interpretation of variants found by diagnostic testing.This study aimed to classify the MLH1 c.1989t5G>A mutation,which was previously reported as a variant of uncertain significance,to describe its clinical phenotypes and characteristics,to enable detailed genetic counselling.Methods:We reviewed the database of patients with Lynch-syndrome gene detection in our hospital.A novel variant of MLH1 c.1989t5G>A identified by next-generation sequencing was further investigated in this study.Immunohistochemical staining was carried out to assess the expression of MLH1 and PMS2 protein in tumour tissue.In silico analysis by Alamut software was used to predict the MLH1 c.1989t5G>A variant function.Reverse transcription-polymerase chain reaction and sequencing of RNA fromwhole bloodwere used to analyse the functional significance of this mutation.Results:Among affected family members in the suspected Lynch-syndrome pedigree,the patient suffered from late-stage colorectal cancer but had a good prognosis.We found the MLH1 c.1989t5G>A variant,which led to aberrant splicing and loss of MLH1 and PMS2 protein in the nuclei of tumour cells.An aberrant transcript was detectable and skipping of MLH1 exon 17 in carriers of MLH1 c.1989t5G>A was confirmed.Conclusions:MLH1 c.1989t5G>A was detected in a cancer family pedigree and identified as a pathological variant in patients with Lynch syndrome.Themutation spectrumof Lynch syndrome was enriched through enhanced genetic testing and close surveillancemight help future patients who are suspected of having Lynch syndrome to obtain a definitive early diagnosis.