“Cold”colorectal cancer faces a bottleneck in immunotherapy

The advent of immunotherapy and the development of immune checkpoint inhibitors(ICIs)are changing the way we think about cancer treatment.ICIs have shown clinical benefits in a variety of tumor types,and ICI-based immunotherapy has shown effective clinical outcomes in immunologically“hot”tumors.However,for immunologically“cold”tumors such as colorectal cancer(CRC),only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates.In this review,we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC,and summarize the treatment strategies and challenges of immunotherapy for cold CRC.We also explain the mechanism,biology,and role of immunotherapy for cold CRC,which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.

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.

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.

Micro RNAs in colorectal cancer:Role in metastasis and clinical perspectives

Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.

Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer

BACKGROUND As one effective treatment for lateral pelvic lymph node(LPLN)metastasis(LPNM),laparoscopic LPLN dissection(LPND)is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery.With regard to improving the accuracy and completeness of LPND as well as safety,we tried an innovative method using indocyanine green(ICG)visualized with a near-infrared(NIR)camera system to guide the detection of LPLNs in patients with middle-low rectal cancer.AIM To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer.METHODS A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision(TME)and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group.Clinical characteristics,operative outcomes,pathological outcomes,and postoperative complication information were compared and analysed between the two groups.RESULTS Compared to the non-ICG group,the ICG group had significantly lower intraoperative blood loss(55.8±37.5 mL vs 108.0±52.7 mL,P=0.003)and a significantly larger number of LPLNs harvested(11.5±5.9 vs 7.1±4.8,P=0.017).The LPLNs of two patients in the non-IVG group were residual during LPND.In addition,no significant difference was found in terms of LPND,LPNM,operative time,conversion to laparotomy,preoperative complication,or hospital stay(P>0.05).CONCLUSION ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.

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.

Natural orifice specimen extraction with laparoscopic radical gastrectomy for distal gastric cancer: A case report

BACKGROUND This article introduces the surgical method and early experience in performing totally laparoscopic radical gastrectomy with transrectal specimen extraction for gastric cancer, and we evaluate the short-term effects and feasibility of this new procedure for gastric cancer in a 64-year-old male patient. This approach may provide new possibilities for gastric natural orifice specimen extraction(NOSE)surgery. In addition, we believe that this new procedure may further relieve pain,speed up recovery, and cause minimal physiological and psychological impact.CASE SUMMARY We performed NOSE gastrectomy in a male patient. Tumor resection, digestive tract reconstruction, and lymph node dissection were performed totally laparoscopically;the specimen was extracted from the natural orifice of the rectum-anus. This procedure reduced damage to the abdominal wall and decreased postoperative pain. We successfully performed radical gastrectomy without conversion and complications. Total operative time and blood loss were 176 min and 50 m L, respectively. The patient resumed normal activities of daily living on day 1 without pain, and passed flatus within 48 h. Postoperative hospital stay was 10 d. The number of resected lymph nodes was 0/43. During the follow-up, no stricture or anastomotic leakage was detected. Three months postoperatively, colonoscopy showed full recovery of the rectum without stricture or scar contracture. Computed tomography and laboratory test results showed no signs of tumor recurrence. There was no visible scar on the abdominal wall.CONCLUSION It is safe and reliable to perform totally laparoscopic radical gastrectomy with transrectal specimen extraction for distal gastric cancer patients.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study

BACKGROUND Brain metastasis(BM)from colorectal cancer(CRC)is rarely encountered clinically,and its prognosis has not been fully evaluated.AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed,using the data from 2010 to 2014 from the Surveillance,Epidemiology,and End Results database.Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models,respectively.A scoring system was developed using the independent prognostic factors,and was used to measure the survival difference among different patients.RESULTS For the 371 patients,the median overall survival was 5 mo,survival rates were 27%at 1 year and 11.2%at 2 years.Prognostic analysis showed that age,carcinoembryonic antigen level and extracranial metastasis to the liver,lung or bone were independent prognostic factors.A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups(scores of 0-1,2-3,and 4).The median survival of patients with scores of 0-1,2-3 and 4 was 14,5 and 2 mo,respectively(P<0.001).Subgroup analysis showed that there were significant differences in prognosis among the groups.Score 2-3 vs 0-1:hazard ratio(HR)=2.050,95%CI:1.363-3.083;P=0.001;score 4 vs 0-1:HR=3.721,95%CI:2.225-6.225;P<0.001;score 2-3 vs 4:HR=0.551,95%CI:0.374-0.812;P=0.003.CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC.These results are helpful in providing a reference for guiding therapy.

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.

Evaluation of clinical significance of claudin 7 and construction of prognostic grading system for stage Ⅱ colorectal cancer

BACKGROUND Claudin 7 is often abnormally expressed in cancers and promotes the progression of some malignancies. However, the role of claudin 7 in stage Ⅱ colorectal cancer(CRC) has not been studied.AIM To assess the expression and prognostic value of claudin 7 in stage Ⅱ CRC.METHODS We retrospectively studied 231 stage Ⅱ CRC patients who underwent radical surgery at our hospital from 2013 to 2014. The protein expression level of claudin7 was assessed and its relationship with clinicopathological features and prognosis was statistically analyzed. The independent prognostic factors were identified by Cox proportional hazards models. A prognostic grading system was constructed to stratify the survival of CRC patients.RESULTS The expression of claudin 7 was significantly reduced in cancer tissues compared with normal tissues(P < 0.001), and its low expression was closely related to recurrence of the disease(P = 0.017). Multivariate analysis confirmed that claudin7 low expression(claudin 7-low)(P = 0.028) and perineural invasion positivity(PNI+)(P = 0.026) were independent predictors of poor disease-free survival(DFS). A prognostic grading system based on the status of claudin 7 and PNI classified the patients into three prognostic grades: grade A(claudin 7-high and PNI-), grade B(claudin 7-low and PNI-, claudin 7-high and PNI+), and grade C(claudin 7-low and PNI+). The DFS was significantly different among the three grades(grade B vs grade A, P = 0.032;grade C vs grade A, P < 0.001;grade C vs grade B, P = 0.040).CONCLUSION Claudin 7 can be used as a new prognostic marker to predict the DFS of patients with stage Ⅱ CRC. The prognostic grading system with the addition of claudin 7 can further improve prognosis stratification of patients.

International consensus on natural orifice specimen extraction surgery(NOSES)for colorectal cancer

In recent years,natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal cancer has attracted widespread attention.The potential benefits of NOSES including reduction in postoperative pain and wound complications,less use of postoperative analgesic,faster recovery of bowel function,shorter length of hospital stay,better cosmetic and psychological effect have been described in colorectal surgery.Despite significant decrease in surgical trauma of NOSES have been observed,the potential pitfalls of this technique have been demonstrated.Particularly,several issues including bacteriological concerns,oncological outcomes and patient selection are raised with this new technique.Therefore,it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery.After three rounds of discussion by all members of the International Alliance of NOSES,the consensus is finally completed,which is also of great significance to the long-term progress of NOSES worldwide.

International consensus on natural orifice specimen extraction surgery(NOSES)for gastric cancer(2019)

At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operative recovery,short hospital stay,and positive psychological impact.However,NOSES for the treatment of gastric cancer(GC)is still in its infancy,and there is great potential to improve its theoretical system and clinical practice.Especially,several key points including oncological outcomes,bacteriological concerns,indication selection,and standardized surgical procedures are raised with this innovative technique.Therefore,it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES,which is of great significance for healthy and orderly development of NOSES worldwide.

Totally laparoscopic resection and natural orifice specimen extraction surgery(NOSES)in synchronous rectal and gastric cancer

Introduction Synchronous gastrointestinal cancer requires simultaneous resection.Recently,natural orifice specimen extraction surgery(NOSES)has become a new procedure of minimally invasive surgery[1].Here,we report the first case of NOSES in the treatment of synchronous rectal and gastric cancer.Case report The patient was a 68-year-old man with a past medical history of hypertension and coronary heart disease.The American Society of Anesthesiologists risk score was II and his body mass index was 28.1 kg/m^(2).The endoscopy examination found a 2-cm lesion in the gastric antrum and 3-cm lesion in the middle rectum.

Laparoscopic radical right hemicolectomy with transrectal-specimen extraction:a novel natural-orifice specimen-extraction procedure

Introduction The main treatment for colon cancer is surgery;however,conventional surgery causes great suffering due to the huge abdominal incision.The advent of laparoscopic surgery has greatly reduced abdominal-wall damage and pain,but anastomosis and the specimen-removal process still require creation of an incision in the abdominal wall.In 1993,Franklin et al.[1]described a case of totally laparoscopic colectomy with transanal specimen extraction as the first natural-orifice specimenextraction surgery(NOSES)and this has been considered the most preferable procedure owing to the absence of abdominal incision,mild post-operative pain,and rapid recovery.

lncRNA-PACER upregulates COX-2 and PGE2 through the NF-κB pathway to promote the proliferation and invasion of colorectal-cancer cells

Background p50-associated cyclooxygenase-2 extragenic RNA(PACER)is a recently identified antisense long non-coding RNA(lncRNA)located on the upstream of the promoter region of cyclooxygenase-2(COX-2).Preliminary studies have suggested that PACER is involved in the regulation of COX-2 expression in macrophagocyte and osteosarcoma cells.However,the role of this lncRNA in colorectal cancer(CRC)remains elusive.Here,we investigated the expression of PACER and its effect on cell proliferation and invasion to explore the role of PACER in CRC.Methods Real-time quantitative PCR(RT-qPCR)analysis was used to evaluate the expression of PACER in CRC tissues and cells.Methyl thiazolyl tetrazolium(MTT)analysis was then used to investigate the inhibition effect of PACER knock-down in cell proliferation.The promoting role of this lncRNA on invasion by CRC cells was analysed by wound-healing assays,colony-formation assay,and transwell assays.We then used fluorescence in situ hybridization(FISH)to establish the subcellular localization of PACER.COX-2 protein levels were quantified by Western blot analysis and grayscale scanning analysis following the knock-down of PACER.Luciferase assay was carried out to monitor the modulation of the COX-2 promoter region by PACER.Tumor xenografts models were used to investigate the impact of PACER on the tumorigenesis of CRC cells in vivo.Enzyme-linked immunosorbent assay(ELISA)was then used to quantify prostaglandin E2(PGE2)production upon knock-down of PACER.Results RT-qPCR analysis revealed that PACER was highly expressed in CRC tissues and cells,and a high PACER-expression level was associated with poor prognosis.MTT assay,wound-healing assay,colony-formation assay,and transwell assay revealed that PACER enhanced CRC-cell proliferation,invasion,and metastasis in vitro.Analysis of lncRNA localization by FISH showed that it mainly resided in the nucleus.RT-qPCR showed that PACER increased mRNA levels of COX-2.Western blot analysis demonstrated,under normal circumstances,that knock-down of PACER decreased the COX-2 protein level.In the case of p50 absence,COX-2 protein increased rapidly and remained highly expressed after knocking down PACER.Luciferase assay revealed that PACER modulated the COX-2 promoter region.Mouse xenograft models of CRC revealed that PACER promoted colorectal tumorigenesis in vivo.ELISA revealed that PACER knock-down inhibited PGE2 production.Conclusions PACER modulates COX-2 expression through the nuclear factor kappa B(NF-jB)pathway in CRC.An increased level of PACER enhances proliferation,migration,and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.

Clinicopathological characteristics and prognostic factors for the recurrence of abdominal desmoid tumors: a retrospective study of 113 patients from two Chinese hospitals

To the Editor:Desmoid tumors(DTs)show local aggressiveness to surrounding structures and exhibit a propensity to recur,leading to a high local recurrence rate and significant functional impairments and morbidity.[1]It has been shown that DTs located in the abdominal wall and abdominal cavity are relatively minimally invasive and have a relatively low recurrence rate,[2]which indicated abdominal desmoid tumors(ADTs)may have different biological make-ups and genes.This study was aimed to delineate the clinicopathological features and determine the prognostic factors for recurrence-free survival(RFS)in ADTs after macroscopic complete surgical resection.

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.

Intra-corporeal delta-shaped anastomosis in laparoscopic right hemicolectomy for right colon cancer:a safe and effective technique

Background and objective:Intra-corporeal delta-shaped anastomosis(IDA)is an important development in laparoscopic digestive-tract reconstruction.We applied it in laparoscopic right hemicolectomy for right colon cancer and compared the short-term outcomes between the patients treated with IDA and conventional extracorporeal anastomosis(EA).Methods:Between 1 January 2016 and 1 October 2017,36 and 50 patients who underwent IDA and EA,respectively,were included.Data on clinicopathological characteristics,surgical outcomes,post-operative recovery and complications were collected and compared between the two groups.Results:Surgical outcomes and clinicopathological characteristics were similar between the two groups except the length of incision,which was significantly shorter in the IDA group than in the EA group(4.660.6 vs 5.660.7 cm,P<0.001).The time to ground activities,fluid diet intake and post-operative hospitalization did not differ between the groups;however,the time to first flatus was significantly shorter in the IDA group than in the EA group(2.860.5 vs 3.260.8 days,P=0.004).The post-operative visual analogue scale for pain was lower in the IDA group than in the EA group on post-operative Day 1(4.060.7 vs 4.561.0,P=0.002)and post-operative Day 3(2.760.6 vs 3.460.6,P<0.001).The surgical complication rates were 8.3 and 16.0%in the IDA and EA groups(P=0.470),respectively.No complications such as anastomotic bleeding,stenosis and leakage occurred in any patient.Conclusions:IDA is safe and feasible and shows more satisfactory short-term outcomes than EA.

Superior mesenteric vessel anatomy features differ in Russian and Chinese patients with right colon cancer:computed tomographybased study

To the Editor:The literature has registered a considerable interest among Western surgeons in the role of extended lymph node dissection in right hemicolectomy.There are a lot of voices of dissent regarding the harvest of nodes lying dorsally to the superior mesenteric vein(SMV)and superior mesenteric artery(SMA).

Upregulated insulin receptor tyrosine kinase substrate promotes the proliferation of colorectal cancer cells via the bFGF/AKT signaling pathway

Background:Some recent studies on insulin receptor tyrosine kinase substrate(IRTKS)have focused more on its functions in diseases.However,there is a lack of research on the role of IRTKS in carcinomas and its mechanism remains ambiguous.In this study,we aimed to clarify the role and mechanism of IRTKS in the carcinogenesis of colorectal cancer(CRC).Methods:We analysed the expression of IRTKS in CRC tissues and normal tissues by researching public databases.Cancer tissues and adjacent tissues of 67 CRC patients who had undergone radical resection were collected from our center.Quantitative real-time polymerase chain reaction and immunohistochemistry were performed in 52 and 15 pairs of samples,respectively.In vitro and in vivo experiments were conducted to observe the effect of IRTKS on CRC cells.Gene Set Enrichment Analysis and Metascape platforms were used for functional annotation and enrichment analysis.We detected the protein kinase B(AKT)phosphorylation and cell viability of SW480 transfected with small interfering RNAs(siRNAs)with or without basic fibroblast growth factor(bFGF)through immunoblotting and proliferation assays.Results:The expression of IRTKS in CRC tissues was higher than that in adjacent tissues and normal tissues(all P<0.05).Disease-free survival of patients with high expression was shorter.Overexpression of IRTKS significantly increased the proliferation rate of CRC cells in vitro and the number of tumor xenografts in vivo.The phosphorylation level of AKT in CRC cells transfected with pLVX-IRTKS was higher than that in the control group.Furthermore,siRNA-IRTKS significantly decreased the proliferation rate of tumor cells and the phosphorylation level of AKT induced by bFGF.Conclusion:IRTKS mediated the bFGF-induced cell proliferation through the phosphorylation of AKT in CRC cells,which may contribute to tumorigenicity in vivo.