BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis(UC),including steroid-dependent and steroid-refractory patients,to achieve and maintain steroid-free remission.However,clinical studies ...BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis(UC),including steroid-dependent and steroid-refractory patients,to achieve and maintain steroid-free remission.However,clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient.Cytapheresis(CAP)is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects.This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients.AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients.METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP.We analyzed the following points:(1)Efficacy of the first course of CAP;(2)Efficacy of the second,third,and fourth courses of CAP in patients who experienced relapses during the observation period;(3)Efficacy of CAP in colonic mucosa;and(4)Long-term efficacy of CAP.Clinical efficacy was evaluated using Lichtiger’s clinical activity index or Sutherland index(disease activity index).Mucosal healing was evaluated using Mayo endoscopic subscore.The primary and secondary endpoints were the rate of achievement of steroidfree remission and the rate of sustained steroid-free remission,respectively.Statistical analysis was performed using the paired t-test and chi-squared test.RESULTS The rates of clinical remission,steroid-free remission,and poor effectiveness after CAP were 69.1%,45.5%,and 30.9%,respectively.There were no significant differences in rate of steroid-free remission between patients with steroiddependent and steroid-refractory UC.The mean disease activity index and Lichtiger’s clinical activity index scores were significantly decreased after CAP(P<0.0001).The rates of steroid-free remission after the second,third,and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%,83.3%,and 60%,respectively.Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP.The rates of sustained steroid-free remission were 68.0%,60.0%,and 56.0%at 12,24,and 36 mo after the CAP.Nine patients(36%)had maintained steroid-free remission throughout the observation period.CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.展开更多
AIM： To report our experience with the use of granulocytapheresis （GCAP） in 14 patients with active steroid-refractory inflammatory bowel disease （IBD） in order to evaluate its efficacy in achieving remission and...AIM： To report our experience with the use of granulocytapheresis （GCAP） in 14 patients with active steroid-refractory inflammatory bowel disease （IBD） in order to evaluate its efficacy in achieving remission and maintaining a long lasting symptom-free period. METHODS： The activity of the disease was evaluated by clinical activity index （CAI） and endoscopic index （EI） in ulcerative colitis （UC）, while by Crohn＇s disease activity index （CDAI） in Crohn＇s disease （CD）. The patients were treated using the AdacolumnTM system, an adsorption column which selectively binds to granulocytes and monocytes. One session/week of GCAP was performed for 5 wk. Steroids were stopped during apheresis. RESULTS： All the patients completed the five-week course showing no complications. At the end of the last session, 93% of patients showed a clinical remission of the disease that persisted for 6 too. Nine months after the end of the treatment, 60% of the cases maintained remission, while 23% of the patients were still in clinical remission after 12 too. CONCLUSION： Even if the number of our patients with steroid-refractory IBDs was not big, we can assert that GCAP is well tolerated and effective, especially in the first six months after the treatment, in a significant percentage of cases. The rate of sustained response drops slightly after 6 mo and significantly after 12 too, however the absence of severe side effects can be a stimulus for further evaluating new schedules of treatment.展开更多
BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical thera...BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.RESULTSIn the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment(mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%,respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.CONCLUSION The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.展开更多
BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis afte...BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after ICI administration,the the-rapeutic importance of local relief of obstruction has not been reported.CASE SUMMARY A 60-year-old female patient with biliary tract carcinoma and peritoneal metastasis developed elevated liver enzymes following four cycles of combined therapy with anti-PD-1(Pembrolizumab)and a tyrosine kinase inhibitor.Magne-tic resonance cholangiopancreatography indicated a thickening of the upper bile duct and pancreatic sections with narrow lumens.Digital peroral cholangioscopy revealed several erosions and surface vessel tortuosities coating the common bile duct.Endoscopic ultrasound revealed disruption of the middle lumen segment,with poorly defined wall structures.Endoscopic retrograde cholangiopancreato-graphy(ERCP)demonstrated mucosal irregularities with tortuous surface vessels along the common bile duct.Angiographic imaging revealed irregular defects in the middle and lower common bile duct segments,while the proximal duct exhibited multifocal stenosis alternating with dilatation.Biopsy samples obtained via ERCP from the elevated mucosal lesions showed dense epithelial inflam-matory cell infiltration,consistent with immune-related cholangitis.Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxy-cholic acid therapy but are difficult to reduce to normal levels.Liver function normalized,and symptoms improved after local treatment for cholestasis(stent implantation).CONCLUSION Stent placement offers prompt alleviation of cholestasis and constitutes an effective therapeutic strategy for managing immune-related cholangitis.展开更多
BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis....BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis.Steroids may not resolve symptoms in all cases.The use of vedolizumab,a humanized monoclonal antibody againstα4β7 integrin has proven effective in cases refractory to standard treatment.CASE SUMMARY We report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab.She developed severe colitis refractory to methylprednisolone,infliximab and mycophenolate mofetil but responded to vedolizumab.CONCLUSION This case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.展开更多
文摘BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis(UC),including steroid-dependent and steroid-refractory patients,to achieve and maintain steroid-free remission.However,clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient.Cytapheresis(CAP)is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects.This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients.AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients.METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP.We analyzed the following points:(1)Efficacy of the first course of CAP;(2)Efficacy of the second,third,and fourth courses of CAP in patients who experienced relapses during the observation period;(3)Efficacy of CAP in colonic mucosa;and(4)Long-term efficacy of CAP.Clinical efficacy was evaluated using Lichtiger’s clinical activity index or Sutherland index(disease activity index).Mucosal healing was evaluated using Mayo endoscopic subscore.The primary and secondary endpoints were the rate of achievement of steroidfree remission and the rate of sustained steroid-free remission,respectively.Statistical analysis was performed using the paired t-test and chi-squared test.RESULTS The rates of clinical remission,steroid-free remission,and poor effectiveness after CAP were 69.1%,45.5%,and 30.9%,respectively.There were no significant differences in rate of steroid-free remission between patients with steroiddependent and steroid-refractory UC.The mean disease activity index and Lichtiger’s clinical activity index scores were significantly decreased after CAP(P<0.0001).The rates of steroid-free remission after the second,third,and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%,83.3%,and 60%,respectively.Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP.The rates of sustained steroid-free remission were 68.0%,60.0%,and 56.0%at 12,24,and 36 mo after the CAP.Nine patients(36%)had maintained steroid-free remission throughout the observation period.CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.
文摘AIM： To report our experience with the use of granulocytapheresis （GCAP） in 14 patients with active steroid-refractory inflammatory bowel disease （IBD） in order to evaluate its efficacy in achieving remission and maintaining a long lasting symptom-free period. METHODS： The activity of the disease was evaluated by clinical activity index （CAI） and endoscopic index （EI） in ulcerative colitis （UC）, while by Crohn＇s disease activity index （CDAI） in Crohn＇s disease （CD）. The patients were treated using the AdacolumnTM system, an adsorption column which selectively binds to granulocytes and monocytes. One session/week of GCAP was performed for 5 wk. Steroids were stopped during apheresis. RESULTS： All the patients completed the five-week course showing no complications. At the end of the last session, 93% of patients showed a clinical remission of the disease that persisted for 6 too. Nine months after the end of the treatment, 60% of the cases maintained remission, while 23% of the patients were still in clinical remission after 12 too. CONCLUSION： Even if the number of our patients with steroid-refractory IBDs was not big, we can assert that GCAP is well tolerated and effective, especially in the first six months after the treatment, in a significant percentage of cases. The rate of sustained response drops slightly after 6 mo and significantly after 12 too, however the absence of severe side effects can be a stimulus for further evaluating new schedules of treatment.
文摘BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.RESULTSIn the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment(mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%,respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.CONCLUSION The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.
文摘BACKGROUND Steroid-refractory immune-related cholangitis,characterized by biliary obstru-ction,can be caused by drugs such as immune checkpoint inhibitors(ICIs).While there a few reports of sclerosing cholangitis after ICI administration,the the-rapeutic importance of local relief of obstruction has not been reported.CASE SUMMARY A 60-year-old female patient with biliary tract carcinoma and peritoneal metastasis developed elevated liver enzymes following four cycles of combined therapy with anti-PD-1(Pembrolizumab)and a tyrosine kinase inhibitor.Magne-tic resonance cholangiopancreatography indicated a thickening of the upper bile duct and pancreatic sections with narrow lumens.Digital peroral cholangioscopy revealed several erosions and surface vessel tortuosities coating the common bile duct.Endoscopic ultrasound revealed disruption of the middle lumen segment,with poorly defined wall structures.Endoscopic retrograde cholangiopancreato-graphy(ERCP)demonstrated mucosal irregularities with tortuous surface vessels along the common bile duct.Angiographic imaging revealed irregular defects in the middle and lower common bile duct segments,while the proximal duct exhibited multifocal stenosis alternating with dilatation.Biopsy samples obtained via ERCP from the elevated mucosal lesions showed dense epithelial inflam-matory cell infiltration,consistent with immune-related cholangitis.Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxy-cholic acid therapy but are difficult to reduce to normal levels.Liver function normalized,and symptoms improved after local treatment for cholestasis(stent implantation).CONCLUSION Stent placement offers prompt alleviation of cholestasis and constitutes an effective therapeutic strategy for managing immune-related cholangitis.
文摘BACKGROUND Dual checkpoint inhibition improves response rates in treatment naive patients with metastatic melanoma compared to monotherapy.However,it confers a higher rate of toxicity,including immune-related colitis.Steroids may not resolve symptoms in all cases.The use of vedolizumab,a humanized monoclonal antibody againstα4β7 integrin has proven effective in cases refractory to standard treatment.CASE SUMMARY We report the case of a 27-year-old female with Stage IVd metastatic melanoma treated with ipilimumab and nivolumab.She developed severe colitis refractory to methylprednisolone,infliximab and mycophenolate mofetil but responded to vedolizumab.CONCLUSION This case report supports vedolizumab use in severe immune related colitis refractory to standard immunosuppression.
