Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.How...Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.展开更多
Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this stud...Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.展开更多
Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the ...Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.展开更多
Background and aims:Gastro-intestinal(GI)symptoms are often experienced by healthy women during menstruation.An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syn...Background and aims:Gastro-intestinal(GI)symptoms are often experienced by healthy women during menstruation.An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease(IBD);however,IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses(IPAA)have not been studied.We aimed to examine the association between GI symptoms before and during menses in patients with IPAA,and to assess factors for exacerbation of GI symptoms in those patients.Methods:Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey.Participants reported on GI symptoms 1–5 days prior to-(pre-menses)and during the days of their menses in recent months.Demographic and clinical variables were obtained through the survey and chart review.Results:One hundred and twenty-eight(21.3%)out of 600 women with IPAA responded to the survey questionnaire.Fortythree(33.5%)were excluded for reasons including post-menopausal(n=25),hysterectomy(n=14)and use of contraceptives(n=4).Abdominal pain(P=0.001),diarrhea(P=0.021),and urgency(P=0.031)were more commonly reported during menses than pre-menses by the participants.Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch(odds ratio=5.67;95%confidence interval:1.41–22.88;P=0.015).Conclusion:GI symptoms such as abdominal pain,diarrhea,and urgency are commonly associated with menses in patients with ileo-anal pouch.Painful menses may be associated with worsening of GI symptoms.展开更多
Backgrounds:Endoscopic stricturotomy(ESt)has been shown to be effective in treating inflammatory bowel disease(IBD)-associated anastomotic strictures.However,the outcome of ESt in benign,non-IBD conditions has not bee...Backgrounds:Endoscopic stricturotomy(ESt)has been shown to be effective in treating inflammatory bowel disease(IBD)-associated anastomotic strictures.However,the outcome of ESt in benign,non-IBD conditions has not been described.The aim of this study was to evaluate the outcome of ESt in the management of IBD and non-IBD-associated strictures.Methods:Data of all consecutive IBD and non-IBD patients with benign anastomotic strictures treated with ESt from 2009 to 2016 were extracted.The primary outcomes were surgery-free survival and procedure-related complications.Results:A total of 49 IBD and 15 non-IBD patients were included in this study.The IBD group included 25 patients with Crohn’s disease and 24 with ulcerative colitis and ileal pouches.Underlying diseases in the non-IBD group included colorectal cancer(n=7),diverticulitis(n=5),large bowel prolapse(n=2),and constipation(n=1).Immediate technical success was achieved in all patients in both groups.Bleeding complications occurred on five occasions(4.7%per procedure)in the IBD group,while no complication occurred in the non-IBD group(P=0.20).Stricture improvement on follow-up endoscopy was found in 10(20.4%)and 5(33.3%)patients in the IBD and non-IBD groups,respectively(P=0.32).Six(12.2%)patients in the IBD group and four(26.7%)patients in the non-IBD group eventually required stricture-related surgery(P=0.23).IBD patients appeared to have a higher tendency formaintaining surgery-free after the procedure than non-IBD patients(P=0.08).Conclusions:Endoscopic stricturotomy was shown to have comparable outcomes,though non-IBD patients seem to have a higher need for subsequent surgery but a lower complication rate than IBD patients.展开更多
Parastomal pyoderma gangrenosum(PPG)is an unusual neutrophilic dermatosis characterized by painful,necrotic ulcerations occurring in the area surrounding an abdominal stoma.It typically affects young to middle-aged ad...Parastomal pyoderma gangrenosum(PPG)is an unusual neutrophilic dermatosis characterized by painful,necrotic ulcerations occurring in the area surrounding an abdominal stoma.It typically affects young to middle-aged adults,with a slight female predominance.The underlying etiology for PPG remains enigmatic but aberrant immune response to injury may play a pivotal role.The reported risk factors for the development of PPG include the presence of extra-intestinal manifestations,autoimmune disorders and obesity,along with local factors,such as the presence of parastomal hernia or pressure ulcer.PPG can develop at any time after the stoma construction.The histopathological features of PPG are not pathognomonic and its diagnosis is mainly based on clinical features.The management of PPG often requires a multidisciplinary approach,with a combination of local wound care and systemic medications.展开更多
Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between...Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.展开更多
基金This work is supported by grants from the National Key Clinical Discipline,National Natural Science Foundation of China(No.81300367 and No.81400604)Guangdong Natural Science Foundation(No.2015A030313108)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.
基金supported by the National Key R&D Program of China[no.2017YFC1308800]the National Natural Science Foundation of China[no.81870383]+1 种基金the Clinical Innovation Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[no.2018GZR0201005]the Science and Technology Planning Project of Guangzhou City[no.201804010014].
文摘Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.
基金supported by National Natural Science Foundation of China(No.81400603)Guangdong Natural Science Foundation(No.2015A030310190)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.
文摘Background and aims:Gastro-intestinal(GI)symptoms are often experienced by healthy women during menstruation.An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease(IBD);however,IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses(IPAA)have not been studied.We aimed to examine the association between GI symptoms before and during menses in patients with IPAA,and to assess factors for exacerbation of GI symptoms in those patients.Methods:Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey.Participants reported on GI symptoms 1–5 days prior to-(pre-menses)and during the days of their menses in recent months.Demographic and clinical variables were obtained through the survey and chart review.Results:One hundred and twenty-eight(21.3%)out of 600 women with IPAA responded to the survey questionnaire.Fortythree(33.5%)were excluded for reasons including post-menopausal(n=25),hysterectomy(n=14)and use of contraceptives(n=4).Abdominal pain(P=0.001),diarrhea(P=0.021),and urgency(P=0.031)were more commonly reported during menses than pre-menses by the participants.Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch(odds ratio=5.67;95%confidence interval:1.41–22.88;P=0.015).Conclusion:GI symptoms such as abdominal pain,diarrhea,and urgency are commonly associated with menses in patients with ileo-anal pouch.Painful menses may be associated with worsening of GI symptoms.
基金Dr Bo Shen is supported by the Ed and Joey Story Endowed ChairThis study was presented as a poster at the American College of Gastroenterology(October 2017,Orlando,Florida).
文摘Backgrounds:Endoscopic stricturotomy(ESt)has been shown to be effective in treating inflammatory bowel disease(IBD)-associated anastomotic strictures.However,the outcome of ESt in benign,non-IBD conditions has not been described.The aim of this study was to evaluate the outcome of ESt in the management of IBD and non-IBD-associated strictures.Methods:Data of all consecutive IBD and non-IBD patients with benign anastomotic strictures treated with ESt from 2009 to 2016 were extracted.The primary outcomes were surgery-free survival and procedure-related complications.Results:A total of 49 IBD and 15 non-IBD patients were included in this study.The IBD group included 25 patients with Crohn’s disease and 24 with ulcerative colitis and ileal pouches.Underlying diseases in the non-IBD group included colorectal cancer(n=7),diverticulitis(n=5),large bowel prolapse(n=2),and constipation(n=1).Immediate technical success was achieved in all patients in both groups.Bleeding complications occurred on five occasions(4.7%per procedure)in the IBD group,while no complication occurred in the non-IBD group(P=0.20).Stricture improvement on follow-up endoscopy was found in 10(20.4%)and 5(33.3%)patients in the IBD and non-IBD groups,respectively(P=0.32).Six(12.2%)patients in the IBD group and four(26.7%)patients in the non-IBD group eventually required stricture-related surgery(P=0.23).IBD patients appeared to have a higher tendency formaintaining surgery-free after the procedure than non-IBD patients(P=0.08).Conclusions:Endoscopic stricturotomy was shown to have comparable outcomes,though non-IBD patients seem to have a higher need for subsequent surgery but a lower complication rate than IBD patients.
基金supported by research grants(to B.S.)from The Broad Foundation and The Crohn’s and Colitis Foundation of America.
文摘Parastomal pyoderma gangrenosum(PPG)is an unusual neutrophilic dermatosis characterized by painful,necrotic ulcerations occurring in the area surrounding an abdominal stoma.It typically affects young to middle-aged adults,with a slight female predominance.The underlying etiology for PPG remains enigmatic but aberrant immune response to injury may play a pivotal role.The reported risk factors for the development of PPG include the presence of extra-intestinal manifestations,autoimmune disorders and obesity,along with local factors,such as the presence of parastomal hernia or pressure ulcer.PPG can develop at any time after the stoma construction.The histopathological features of PPG are not pathognomonic and its diagnosis is mainly based on clinical features.The management of PPG often requires a multidisciplinary approach,with a combination of local wound care and systemic medications.
基金This work was supported by National Key Clinical Discipline,National Natural Science Foundation of China(No.81870383)Guangdong Natural Science Foundation(No.2017A030313785)+1 种基金Science and Technology Planning Project of Guangzhou City(No.201804010014)Science and Technology Planning Project of Guangdong Province(No.2015B020229001).
文摘Background:This study sought to evaluate the risk factors for the development of colitis-associated neoplasia(CAN)in Chinese patients with inflammatory bowel disease(IBD).Methods:IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers.In addition to initial pathology evaluation,a CAN diagnosis was confirmed by two expert pathologists.Patients with CAN(n=29)were compared with non-CAN controls(n=87).Matching was performed for gender and IBD type with a ratio of three controls to one subject.Results:Of the 29 patients with CAN,8(27.6%)had colorectal cancer(CRC),20(69.0%)had a final diagnosis of low-grade dysplasia and 1(3.4%)had high-grade dysplasia.Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN,with odds ratios of 1.09[95%confidence interval(CI):1.04–1.14,P<0.001]and 1.14(95%CI:1.03–1.27,P=0.013),respectively.Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis(P=0.012)and had longer IBD durations(P=0.019).Conclusions:Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.
