BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung diseas...BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with PCM.CASE SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody stools.Computed tomography revealed pleural effusion and ascites.Pleural effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were negative.Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis.Echocardiography revealed enlarged atria and reduced left ventricular systolic function.The diagnosis remained unclear.Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels.Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type.Smear cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested PCM.Flow cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and CD117.Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal abnormalities.Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining.The patient was finally diagnosed with PCM.CONCLUSION A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.展开更多
AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.M...AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.展开更多
Intestinal Behcet＇s disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and Ueo...Intestinal Behcet＇s disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and Ueocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet＇s disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.展开更多
Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at t...Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.展开更多
Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the c...Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 （HSP70） and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.展开更多
Inflammatory bowel disease (IBD) is regarded as one of the risk factors for colorectal cancer, and early detection of cancer in these patients may be difficult, especially in pediatric patients. Prognosis of pediatric...Inflammatory bowel disease (IBD) is regarded as one of the risk factors for colorectal cancer, and early detection of cancer in these patients may be difficult, especially in pediatric patients. Prognosis of pediatric colorectal cancer is known to be poor, because of delayed diagnosis and unfavorable differentiation. We report a case of a pediatric patient with a 10-year history of ulcerative colitis who was diagnosed with sigmoid colon cancer when he was 15 years old. He underwent proctocolectomy with ileal pouch anal anastomosis. Postoperative pathological examination of the tumor revealed adenocarcinoma. The pericolic tissue layer was infiltrated, but metastases were not found in either of the two lymph nodes. Children with a long history of predisposing factors such as IBD need particular attention to the possibility of colorectal cancer. Early diagnosis through regular screening with colonoscopy is one of the most important critical factors for a good prognosis.展开更多
BACKGROUND Severe total colonic necrosis,septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening.No such severe complications have been reported in the literature.CAS...BACKGROUND Severe total colonic necrosis,septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening.No such severe complications have been reported in the literature.CASE SUMMARY We report a 36-year-old woman who developed total colonic necrosis and septic shock secondary to UC.The patient was treated with emergency surgery because computed tomography showed suspicious perforations.Persistent massive ascites occurred after operation and computed tomography angiography demonstrated portal vein,mesenteric vein and splenic vein thrombosis.The patient was discharged from hospital after active treatment.CONCLUSION Clinicians should pay attention to venous thrombosis,colonic necrosis and septic shock in UC patients.Close observation of surgical indications and timely surgical intervention are the key to reduce mortality and complications in UC.展开更多
This report describes a young female in her secondtrimester of pregnancy with known ulcerative colitis onmaintenance medical therapy. She was admitted forabdominal pain, and workup revealed a colonic stric-ture and ul...This report describes a young female in her secondtrimester of pregnancy with known ulcerative colitis onmaintenance medical therapy. She was admitted forabdominal pain, and workup revealed a colonic stric-ture and ulceration with contained perforation. Aftermultidisciplinary discussion she was managed withcolectomy and end ileostomy. She delivered a healthynewborn 18 wk after surgery. Only a few prior reportsdescribed surgical management of inflammatory boweldisease during pregnancy, with recent results indicatinglow risk of adverse outcomes.展开更多
AIM To examine whether second generation of colon capsule endoscopy(CCE-2) is acceptable for assessing the severity of mucosal inflammation and evaluating mucosal healing using CCE-2 is able to predict outcome in ulce...AIM To examine whether second generation of colon capsule endoscopy(CCE-2) is acceptable for assessing the severity of mucosal inflammation and evaluating mucosal healing using CCE-2 is able to predict outcome in ulcerative colitis(UC) patients, especially in clinical remission.METHODS A total of 30 consecutive UC patients in clinical remission were enrolled to undergo CCE-2. Clinical remission was defined as clinical activity index(CAI) ≤ 4 according to Rachmilewitz index. The rate of total colon observation and colon cleansing level were evaluated. Severity of mucosal inflammation in UC was assessed according to the Mayo endoscopic subscore(MES) and Ulcerative Colitis Endoscopic Index of Severity(UCEIS). Relapsefree survival was assessed. Acceptability of CCE-2 was assessed using a questionnaire survey.RESULTS The rate of total colon observation within its battery life was 93.3%. The proportion of "excellent" plus "good" cleansing level was 73.3%. The rate of mucosal healing(MES 0, 1) assessed by CCE-2 was 77.0%. The relapse-free survival rate was significantly higher in MES 0, 1 than in MES 2, 3(P = 0.0435), and in UCEIS 0-3 than in UCEIS 4-8(P = 0.0211), whereas there was no significant difference between CAI 0 and CAI 1-4 groups. A questionnaire survey revealed an overall acceptability of CCE.CONCLUSION CCE-2 is acceptable for assessing the severity of mucosal inflammation in UC patients, especially in clinical remission. Evaluating mucosal healing using CCE-2 was able to predict outcome.展开更多
BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid a...BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS:Four months after total procto-colectomy for a rectal adenocarcinoma(Astler-Coller C2),a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal,but alpha- fetoprotein was 32 000μg/L.Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS:Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT.The patient was well during the first 6 months and refused any adjuvant chemotherapy.He died from liver failure 19 months after initial diagnosis. CONCLUSIONS:HT is a rare colon cancer.The preoperative diagnosis of this tumor requires a high degree of suspicion,the availability of a panel of immunohistochemical markers,and a certain amount of luck.The prognosis is poor despite an aggressive andmultimodal therapeutic strategy.So far,none of the hypotheses proposed about the origin and the biology of these tumors is convincing.展开更多
Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the d...Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the development of intestinal inflammation. To evaluate contributions of Helicobacter in inflammatory bowel disease, we investigated whether and how pre-existing intestinal colonization would affect disease severity and biomarkers of inflammation in experimental IBD. Materials and Methods: Mice were infected with H. muridarum 2 weeks prior to induction of colitis mediated by 3% dextran sulfate (DSS). Disease activity index, stool blood and consistency, colon length, myeloperoxidase, histopathology, blood and lymphatic vessels, and numbers of dilated mucosal crypts were measured in control, DSS-only, H. muridarum-infected, and H. muridarum-infected + DSS mice. Results: Prior to DSS challenge, H. muridarum-infected mice showed little distal gut injury by several indices of colon inflammation with decreased blood vessel density in the submucosa, and lower lymphatic density in the mucosa and submucosa. However, after DSS colitis, H. muridarum-infected mice exhibited significantly greater disease. Weight change, stool bleeding, diarrhea, and angiogenesis were all increased in H. muridarum-infected mice in DSS colitis compared to DSS controls. Conclusions: Our data show that Helicobacter colonization of the intestine, unlike that of the stomach, lowers basal gut inflammatory scores, but increases disease activity and inflammation in an acute colitis model. Intestinal Helicobacter infection may therefore represent a significant sub-clinical factor which predisposes the gut to inflammatory injury.展开更多
The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early...The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accurate assessment of the surveillance effectiveness of colonoscopy and multi-site biopsy protocols. Although the clinical challenge posed to even the most experienced clinicians remains significant, evolving methods of endoscopic imaging may facilitate better evaluation of this highly select group of patients.展开更多
Introduction： Histoplasmosis is a rare infectious condition caused by the fungus Histoplasma capsulatum that can be presented from asymptomatic to severe forms. Tuberculosis, still an endemic infection in some develo...Introduction： Histoplasmosis is a rare infectious condition caused by the fungus Histoplasma capsulatum that can be presented from asymptomatic to severe forms. Tuberculosis, still an endemic infection in some developing countries, can also have variable clinical presentations. Both diseases involve the lungs mostly, but in immunocompromised patients, especially those with advanced HIV infection and transplant patients, disseminated forms are more frequently found. Gastrointestinal involvement is unusual, and digestive bleeding is an even rarer complication. Case presentation： We report the case of a 39-year-old female who was diagnosed with a Mycobacterium tuberculosis and Histoplasma capsulatum coinfection occurring 11 years after a living-donor-related renal transplant. The patient presented a severe gastrointestinal bleeding caused by an ulcer in the ascending colon. She improved after a combined treatment with tuberculostatic and fungicidal drugs. Conclusions： Simultaneous gastrointestinal involvement by histoplasmosis and tuberculosis, presenting as severe digestive bleeding, with minimal respiratory symptoms associated, make this an extremely rare case and a diagnostic challenge. Therefore, it is important to keep a high clinical suspicion of opportunistic infection, especially in immunocompromised patient who presents with LGB.展开更多
The colorectal mucosa includes two quantitatively, structurally and functionally dissimilar areas: one, built with columnar and goblet cells, covers the vast majority of the mucosa, and the other consists of scattered...The colorectal mucosa includes two quantitatively, structurally and functionally dissimilar areas: one, built with columnar and goblet cells, covers the vast majority of the mucosa, and the other consists of scattered minute gut-associated lymphoid tissue (GALT). The overwhelming majority of colorectal carcinomas evolve in GALT-free mucosal areas and very rarely in GALT aggregates. Remarkably, the colonic mucosa in patients with ulcerative colitis (UC) displays a high number of newly formed GALT-aggregates. The patient here described is a 68-year-old female with a history of UC since 1984. At surveillance colonoscopy in 2012, one of two detected polyps was a tubular adenoma with high-grade dysplasia. Beneath this adenoma, a well-circumscribed GALT sheltering a carcinoma was found. Serial sections revealed no connection between the villous adenomaand the GALT-carcinoma. The GALT-carcinoma here reported seems to have evolved in a newly formed, UC- dependent, GALT complex. This notion is substantiated by the fact that 27% or 4 out of the 15 cases of GALT- carcinomas in the colon reported in the literature (including the present case) evolved in patients with UC.展开更多
AIM To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease(IBD). METHODS Colorectal samples were obtained from patients unde...AIM To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease(IBD). METHODS Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or rectosigmoidoscopy. Patients diagnosed with ulcerativecolitis(n = 18) or Crohn's disease(n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group(CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, doublelabeled confocal microscopy was used. RESULTS Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive(-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and noninflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels. CONCLUSION Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.展开更多
OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inh...OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.展开更多
Ibuprofen is a relatively safe anti inflammatory drug among other NSAIDs. However, frequent and long-term administration of ibuprofen in conventional oral preparation is still considered for ulceration. As previously ...Ibuprofen is a relatively safe anti inflammatory drug among other NSAIDs. However, frequent and long-term administration of ibuprofen in conventional oral preparation is still considered for ulceration. As previously reported, the daily administration of the ibuprofen orally for 14 days in rats caused the gastroduodenal ulcer. Several mechanisms have been reported: the suppression of the gastric prostaglandin synthesis and the local irritant effect on epithelium due to the direct contact of drug with mucosal wall. In this work, developed ibuprofen pellet with double coatings aimed to release ibuprofen only when reaching colonic compartment. The results of pharmacokinetic study reported previously suggested that this might be a successful target. Present study described the potential benefits of this formula in exhibiting effective local anti inflammatory action in colon. Male Wistar rats were induced for ulcerative colitis with 2,4,6-trinitrobenzene sulfonic acid. Twenty four hours after induction, treatments were given using either ibuprofen suspension or pellet for 14 days. Ulcerations were observed visually, with gross anatomic and microscopic examinations. Group treated with ibuprofen pellet showed best recovery nearly close to healthy group. Moreover, the group did not develop ulceration in upper part of GIT. Colonic targeted ibuprofen pellet showed most effective local antiinflammatory action and at the same time reduced the ulcer formation in the upper part of GIT.展开更多
文摘BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with PCM.CASE SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody stools.Computed tomography revealed pleural effusion and ascites.Pleural effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were negative.Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis.Echocardiography revealed enlarged atria and reduced left ventricular systolic function.The diagnosis remained unclear.Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels.Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type.Smear cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested PCM.Flow cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and CD117.Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal abnormalities.Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining.The patient was finally diagnosed with PCM.CONCLUSION A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.
文摘AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.
文摘Intestinal Behcet＇s disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and Ueocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet＇s disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.
基金supported by National Key Research and Development Program of China(No.2017YFC1308800)Industry-University-Research Innovation Fund in Ministry of Education of the People’s Republic of China(No.2018A01013)。
文摘Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.
基金the National Basic Research Program of China (973 Program),No.2009CB522900the Shanghai Leading Academic Discipline Project,No.S30304
文摘Pathological changes in the colon are closely associated with the spinal cord, and innervation of spinal cord can regulate cellular functions. Our previous studies verified that moxibustion protects and restores the colonic mucosa, but the mechanisms of action remain unknown. The present study observed the effects of moxibustion and salicylazosulfapyridine on expression of heat-shock protein 70 （HSP70） and its mRNA in the spinal cord and colonic mucosa of ulcerative colitis rats. Results demonstrated that moxibustion and salicylazosulfapyridine increased HSP70 mRNA expression in the spinal cord and colonic mucosa of ulcerative colitis rats. The decreased transcriptional activity of HSP70 in the spinal cord and colonic mucosa might participate in damage to the colonic mucosa in ulcerative colitis rats. Moxibustion exerted protective effects on colonic mucosa by up-regulating HSP70 transcriptional activity in the spinal cord and colonic mucosa.
文摘Inflammatory bowel disease (IBD) is regarded as one of the risk factors for colorectal cancer, and early detection of cancer in these patients may be difficult, especially in pediatric patients. Prognosis of pediatric colorectal cancer is known to be poor, because of delayed diagnosis and unfavorable differentiation. We report a case of a pediatric patient with a 10-year history of ulcerative colitis who was diagnosed with sigmoid colon cancer when he was 15 years old. He underwent proctocolectomy with ileal pouch anal anastomosis. Postoperative pathological examination of the tumor revealed adenocarcinoma. The pericolic tissue layer was infiltrated, but metastases were not found in either of the two lymph nodes. Children with a long history of predisposing factors such as IBD need particular attention to the possibility of colorectal cancer. Early diagnosis through regular screening with colonoscopy is one of the most important critical factors for a good prognosis.
文摘BACKGROUND Severe total colonic necrosis,septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening.No such severe complications have been reported in the literature.CASE SUMMARY We report a 36-year-old woman who developed total colonic necrosis and septic shock secondary to UC.The patient was treated with emergency surgery because computed tomography showed suspicious perforations.Persistent massive ascites occurred after operation and computed tomography angiography demonstrated portal vein,mesenteric vein and splenic vein thrombosis.The patient was discharged from hospital after active treatment.CONCLUSION Clinicians should pay attention to venous thrombosis,colonic necrosis and septic shock in UC patients.Close observation of surgical indications and timely surgical intervention are the key to reduce mortality and complications in UC.
文摘This report describes a young female in her secondtrimester of pregnancy with known ulcerative colitis onmaintenance medical therapy. She was admitted forabdominal pain, and workup revealed a colonic stric-ture and ulceration with contained perforation. Aftermultidisciplinary discussion she was managed withcolectomy and end ileostomy. She delivered a healthynewborn 18 wk after surgery. Only a few prior reportsdescribed surgical management of inflammatory boweldisease during pregnancy, with recent results indicatinglow risk of adverse outcomes.
文摘AIM To examine whether second generation of colon capsule endoscopy(CCE-2) is acceptable for assessing the severity of mucosal inflammation and evaluating mucosal healing using CCE-2 is able to predict outcome in ulcerative colitis(UC) patients, especially in clinical remission.METHODS A total of 30 consecutive UC patients in clinical remission were enrolled to undergo CCE-2. Clinical remission was defined as clinical activity index(CAI) ≤ 4 according to Rachmilewitz index. The rate of total colon observation and colon cleansing level were evaluated. Severity of mucosal inflammation in UC was assessed according to the Mayo endoscopic subscore(MES) and Ulcerative Colitis Endoscopic Index of Severity(UCEIS). Relapsefree survival was assessed. Acceptability of CCE-2 was assessed using a questionnaire survey.RESULTS The rate of total colon observation within its battery life was 93.3%. The proportion of "excellent" plus "good" cleansing level was 73.3%. The rate of mucosal healing(MES 0, 1) assessed by CCE-2 was 77.0%. The relapse-free survival rate was significantly higher in MES 0, 1 than in MES 2, 3(P = 0.0435), and in UCEIS 0-3 than in UCEIS 4-8(P = 0.0211), whereas there was no significant difference between CAI 0 and CAI 1-4 groups. A questionnaire survey revealed an overall acceptability of CCE.CONCLUSION CCE-2 is acceptable for assessing the severity of mucosal inflammation in UC patients, especially in clinical remission. Evaluating mucosal healing using CCE-2 was able to predict outcome.
文摘BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS:Four months after total procto-colectomy for a rectal adenocarcinoma(Astler-Coller C2),a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal,but alpha- fetoprotein was 32 000μg/L.Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS:Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT.The patient was well during the first 6 months and refused any adjuvant chemotherapy.He died from liver failure 19 months after initial diagnosis. CONCLUSIONS:HT is a rare colon cancer.The preoperative diagnosis of this tumor requires a high degree of suspicion,the availability of a panel of immunohistochemical markers,and a certain amount of luck.The prognosis is poor despite an aggressive andmultimodal therapeutic strategy.So far,none of the hypotheses proposed about the origin and the biology of these tumors is convincing.
文摘Background: Helicobacter species are best known for their roles in the pathology of gastritis;however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the development of intestinal inflammation. To evaluate contributions of Helicobacter in inflammatory bowel disease, we investigated whether and how pre-existing intestinal colonization would affect disease severity and biomarkers of inflammation in experimental IBD. Materials and Methods: Mice were infected with H. muridarum 2 weeks prior to induction of colitis mediated by 3% dextran sulfate (DSS). Disease activity index, stool blood and consistency, colon length, myeloperoxidase, histopathology, blood and lymphatic vessels, and numbers of dilated mucosal crypts were measured in control, DSS-only, H. muridarum-infected, and H. muridarum-infected + DSS mice. Results: Prior to DSS challenge, H. muridarum-infected mice showed little distal gut injury by several indices of colon inflammation with decreased blood vessel density in the submucosa, and lower lymphatic density in the mucosa and submucosa. However, after DSS colitis, H. muridarum-infected mice exhibited significantly greater disease. Weight change, stool bleeding, diarrhea, and angiogenesis were all increased in H. muridarum-infected mice in DSS colitis compared to DSS controls. Conclusions: Our data show that Helicobacter colonization of the intestine, unlike that of the stomach, lowers basal gut inflammatory scores, but increases disease activity and inflammation in an acute colitis model. Intestinal Helicobacter infection may therefore represent a significant sub-clinical factor which predisposes the gut to inflammatory injury.
文摘The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accurate assessment of the surveillance effectiveness of colonoscopy and multi-site biopsy protocols. Although the clinical challenge posed to even the most experienced clinicians remains significant, evolving methods of endoscopic imaging may facilitate better evaluation of this highly select group of patients.
文摘Introduction： Histoplasmosis is a rare infectious condition caused by the fungus Histoplasma capsulatum that can be presented from asymptomatic to severe forms. Tuberculosis, still an endemic infection in some developing countries, can also have variable clinical presentations. Both diseases involve the lungs mostly, but in immunocompromised patients, especially those with advanced HIV infection and transplant patients, disseminated forms are more frequently found. Gastrointestinal involvement is unusual, and digestive bleeding is an even rarer complication. Case presentation： We report the case of a 39-year-old female who was diagnosed with a Mycobacterium tuberculosis and Histoplasma capsulatum coinfection occurring 11 years after a living-donor-related renal transplant. The patient presented a severe gastrointestinal bleeding caused by an ulcer in the ascending colon. She improved after a combined treatment with tuberculostatic and fungicidal drugs. Conclusions： Simultaneous gastrointestinal involvement by histoplasmosis and tuberculosis, presenting as severe digestive bleeding, with minimal respiratory symptoms associated, make this an extremely rare case and a diagnostic challenge. Therefore, it is important to keep a high clinical suspicion of opportunistic infection, especially in immunocompromised patient who presents with LGB.
文摘The colorectal mucosa includes two quantitatively, structurally and functionally dissimilar areas: one, built with columnar and goblet cells, covers the vast majority of the mucosa, and the other consists of scattered minute gut-associated lymphoid tissue (GALT). The overwhelming majority of colorectal carcinomas evolve in GALT-free mucosal areas and very rarely in GALT aggregates. Remarkably, the colonic mucosa in patients with ulcerative colitis (UC) displays a high number of newly formed GALT-aggregates. The patient here described is a 68-year-old female with a history of UC since 1984. At surveillance colonoscopy in 2012, one of two detected polyps was a tubular adenoma with high-grade dysplasia. Beneath this adenoma, a well-circumscribed GALT sheltering a carcinoma was found. Serial sections revealed no connection between the villous adenomaand the GALT-carcinoma. The GALT-carcinoma here reported seems to have evolved in a newly formed, UC- dependent, GALT complex. This notion is substantiated by the fact that 27% or 4 out of the 15 cases of GALT- carcinomas in the colon reported in the literature (including the present case) evolved in patients with UC.
文摘AIM To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease(IBD). METHODS Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or rectosigmoidoscopy. Patients diagnosed with ulcerativecolitis(n = 18) or Crohn's disease(n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group(CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, doublelabeled confocal microscopy was used. RESULTS Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive(-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and noninflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels. CONCLUSION Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.
基金supported by National Natural Science Foundation of China(81273606,81473259 to XL,81603116 to YS)National Science and Technology Major Project(2014ZX09J14103-08C to XL)
文摘OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.
文摘Ibuprofen is a relatively safe anti inflammatory drug among other NSAIDs. However, frequent and long-term administration of ibuprofen in conventional oral preparation is still considered for ulceration. As previously reported, the daily administration of the ibuprofen orally for 14 days in rats caused the gastroduodenal ulcer. Several mechanisms have been reported: the suppression of the gastric prostaglandin synthesis and the local irritant effect on epithelium due to the direct contact of drug with mucosal wall. In this work, developed ibuprofen pellet with double coatings aimed to release ibuprofen only when reaching colonic compartment. The results of pharmacokinetic study reported previously suggested that this might be a successful target. Present study described the potential benefits of this formula in exhibiting effective local anti inflammatory action in colon. Male Wistar rats were induced for ulcerative colitis with 2,4,6-trinitrobenzene sulfonic acid. Twenty four hours after induction, treatments were given using either ibuprofen suspension or pellet for 14 days. Ulcerations were observed visually, with gross anatomic and microscopic examinations. Group treated with ibuprofen pellet showed best recovery nearly close to healthy group. Moreover, the group did not develop ulceration in upper part of GIT. Colonic targeted ibuprofen pellet showed most effective local antiinflammatory action and at the same time reduced the ulcer formation in the upper part of GIT.
