Advancing the precision management of inflammatory bowel disease in the era of omics approaches and new technology

There is great heterogeneity among inflammatory bowel disease(IBD)patients in terms of pathogenesis,clinical manifestation,response to treatment,and prognosis,which requires the individualized and precision management of patients.Many studies have focused on prediction biomarkers and models for assessing IBD disease type,activity,severity,and prognosis.During the era of biologics,how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics.Multiomics is a promising area for investigating the complex network of IBD pathogenesis.Integrating numerous amounts of data requires the use of artificial intelligence.

VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice

AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing method.RESULTS VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.

Cronkhite-Canada syndrome:Report of six cases and review of literature

Cronkhite-Canada syndrome(CCS)is a rare nonfamilial polyposis syndrome characterized by epithelial disturbances in the gastrointestinal tract and skin.The aim of this study was to investigate the clinical features and potential therapies for CCS.Six patients with CCS admitted from December 1992 to July 2008 to Peking Union Medical College Hospital were evaluated.All patients had clinical manifestation of nonhereditary gastrointestinal polyposis with diarrhea,skin hyperpigmentation,alopecia,and nail dystrophy.Fecal occult blood was positive in all six cases.Serum hemoglobin,potassium,calcium and protein were below the normal range in two cases.Anti-Saccharomyces cerevisiae and antinuclear antibodies were present in three cases.Multiple polyps were found in all patients by gastroscopy and colonoscopy,with only one in the esophagus.Histologically,there were hyperplastic polyps in five cases,tubular adenoma in three,and juvenile polyp in one with chronic inflammation and mucosal edema.Comprehensive treatment led by corticosteroids can result in partial remission of clinical symptoms,and longterm follow-up is necessary.

Corticosteroid therapy in ulcerative colitis:Clinical response and predictors

AIM:To evaluate clinical response to initial corticosteroid(CS) treatment in Chinese ulcerative colitis patients(UC) and identify predictors of clinical response.METHODS:Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China,and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors.Short-term outcomes within one month were classified as primary response and primary non-response.Longterm outcomes within one year were classified as prolonged CS response,CS dependence and secondary non-response.CS refractoriness included primary and secondary non-response.Multivariate analyses were performed to identify predictors associated with clinical response.RESULTS:Within one month,95.0%and 5.0%of the cases were classified into primary response andnon-response,respectively.Within one year,41.6%of cases were assessed as prolonged CS response,while49.5%as CS dependence and 4.0%as secondary nonresponse.The rate of CS refractoriness was 8.9%,while the cumulative rate of surgery was 6.9%within one year.After multivariate analysis of all the variables,tenesmus was found to be a negative predictor of CS dependence(OR=0.336;95%CI:0.147-0.768;P=0.013)and weight loss as a predictor of CS refractoriness(OR=5.662;95%CI:1.111-28.857;P=0.040).After one-month treatment,sustained high Sutherland score(≥6)also predicted CS dependence(OR=2.347;95%CI:0.935-5.890;P=0.014).CONCLUSION:Tenesmus was a negative predictor of CS dependence,while weight loss and sustained high Sutherland score were strongly associated with poor CS response.

Association between CYP24A1 polymorphisms and the risk of colonic polyps and colon cancer in a Chinese population

AIM To determine the pathogenesis and potential single nucleotide polymorphisms(SNPs) as screening sites for colonic polyps,colon cancer and ulcerative colitis,and to analyze the possible association between these genetic polymorphisms and the three diseases. METHODS We evaluated genetic polymorphisms in 144 newly diagnosed colonic polyp patients,96 colon cancer patients and 44 ulcerative colitis patients. The four SNPs genotyped were rs4809957,rs6068816,rs6091822 and rs8124792. The control group consisted of 504 East Asians enrolled in the 1000 Genomes Project. Correlations between CYP24A1 SNPs and the diseases were analyzed by Fisher's exact probability test.RESULTS CYP24A1 polymorphisms rs4809957 A/G and rs6068816 C/T showed a statistically significant association with risk of the three diseases,when both the genotypes and allele frequencies were considered. With regard to rs6091822 G/T,all three diseases were related to risk allele carriers(GT + TT) vs wild-type(GG),but the associations between the allele frequencies and the diseases were not significant. The risk of colonic polyps and colon cancer was related to the allele frequencies of rs8124792 G/A,and this association remained for genotype frequencies of this SNP. CONCLUSION Four SNPs are related to the risk of colonic polyps and colon cancer. G allele in rs6091822 G/T may play an anti-cancer role only if it is homozygous. The A allele,which is a minor component of rs8124792,may be indicated in the diagnosis of colonic polyps or colon cancer rather than ulcerative colitis.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis

Human cytomegalovirus(CMV) is a herpesvirus,which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However,CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis,portal hypertensionrelated ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation,and suggests that testing for CMV should be carried out,even in patients with normal immune status,presenting with severe liver damage or cholestasis.

EFFECTS OF ENTERAL AND PARENTERAL NUTRITION ON GASTROENTERIC HORMONES AND GASTRIC MOTILITY AFTER SUBTOTAL GASTRECTOMY

Objective To investigate the effects of enteral nutrition （EN） and parenteral nutrition （PN） on gastric motility and gastroentefic hormones after subtotal gastrectomy. Methods Forty-one patients underwent gastrectomy were randomly divided into EN group （n=20） and PN group （n=21 ）. From the first postoperative day to the seventh day, patients received either EN （EN group） or PN （PN group） with isocalofic （84.9kJ·kg^-1·d^-1） and isonitrogenous （0.11g·kg^-1·d^-1） intake. Serum gastrin （GAS）, plasma mofilin （MTL）, and plasma cholecystokinin （CCK） were measured on preoperative day, the first and seventh postoperative day. Electrogastrography （EGG） was measured on preoperative day and the seventh postoperative day. Results Compared with preoperafion, blood GAS, MTL, and CCK levels of 41 patients decreased significantly on the first day after subtotal gastrectomy （ P 〈 0. 001 ）, but returned to the preoperative levels one week later. EGG after gastrectomy showed that gastric basal electrical rhythm was significantly restrained （ P 〈 0. 001 ）. On the seventh day after subtotal gastrectomy, plasma MTL and CCK levels in EN group were higher than those in PN group （ P 〈 0.05 ）. There was no difference in GAS level between two groups. EGG in EN group was better than that in PN group postoper- atively. Conclusions The levels of gastroentefitic hormones and the gastric motility decrease significantly after subtotal gastrectomy. In contrast with PN, EN can accelerate the recovery of MTL, CCK, and gastric motility after subtotal gastrectomy.

Establishment of risk model for pancreatic cancer in Chinese Han population

AIM： To investigate risk factors for pancreatic cancer and establish a risk model for Han population. METHODS： This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio （ORs）, 95% confidence intervals （CIs） and 113 value, which were further used to establish the risk model. RESULTS： According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers （not more than 17 pack-years） （OR 1.98; 95% CI 1.11-3.49, P=0.017）. More importantly, heavy smokers in men had increased risk for developing pancreatic cancer （OR 2.11; 95% CI 1.18-3.78, P=0.012） than women. Heavy alcohol drinkers （〉20 cup-years） had increased risk for pancreatic cancer （OR 3.68; 95% CI 1.60-8.44）. Daily diet with high meat intake was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% （P= 0.0003）. Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its importance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer.CONCLUSION： Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Han population has been established with an 88.9% sensitivity and a 97.6% specificity.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis:A case report and review of the literature

BACKGROUND Autoimmune enteropathy(AIE)and primary biliary cholangitis(PBC)are both immune-mediated diseases.AIE or PBC complicated with ulcerative colitis(UC)are rare.There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before,and the pathogenesis of these comorbidities has not been revealed.CASE SUMMARY A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease,and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016.A few months after the neoileostomy,she began to suffer from recurrent episodes of watery diarrhea.She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect.However,her symptoms of diarrhea relapsed in 2019,with different histological features of endoscopic biopsies compared with 2016,which showed apoptotic bodies,a lack of goblet and Paneth cells,and villous blunting.A diagnosis of AIE was established,and the patient’s stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d.Meanwhile,her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC,and treatment with ursodeoxycholic acid(16 mg/kg per day)achieved satisfactory results.CONCLUSION Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients.Continuous follow-up is essential for UC patients with postoperative complications.

Jejunal cavernous lymphangioma manifested as gastrointestinal bleeding with hypogammaglobulinemia in adult: A case report and literature review

BACKGROUND Lymphangioma is a benign lesion that rarely involves the gastrointestinal tract,especially in adults.Small bowel lymphangioma is a rare cause of gastrointestinal bleeding.Here,we report a case of an adult diagnosed with jejunal lymphangioma presenting with melena,anemia and hypogammaglobulinemia.We also summarize and analyze all 23 reported cases from 1961 to 2019,and propose an algorithm for identification and management of small bowel lymphangioma.CASE SUMMARY A case of a 29-year-old woman presented with persistent melena and irondeficiency anemia,accompanied by hypogammaglobulinemia.No lesions were found in the initial workup with esophagogastroduodenoscopy,colonoscopy and computed tomography(CT)enterography.Ultimately,capsule endoscopy and double-balloon enteroscopy revealed a 3 cm×2 cm primary lesion with intensive white lymphatic dilatatory changes and visible fresh blood stains,accompanied by a small satellite lesion.The patient underwent complete surgical resection of these lesions,and histopathological examination confirmed a diagnosis of cavernous lymphangioma of the jejunum.The patient showed no evidence of disease at the time of this report.CONCLUSION We recommend CT,capsule endoscopy and enteroscopy to identify the lesions of lymphangioma.Laparoscopic surgery with histological diagnosis is an ideal curative method.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing

Background:Imbalance of intestinal microbiota was closely related to colitis.Under these circumstances,regulation of enteric flora may be beneficial to the repair of inflammation.We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus),prebiotics and their combination on inflammation,and microflora in mice of acute colitis.Methods:C57BL/6J mice were divided into six groups randomly (blank control group,model control group,probiotics group,synbiotics group,lactitol group and probiotics + lactitol group).Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group.Except for the model control group,the other four groups were intervened with probiotics,synbiotics (probiotics and inulin),lactitol,and probiotics + lactitol.Mice were sacrificed after 1 week of gavage,and pathologic scores were calculated.The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing.Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA),respectively.ANOVA,Tukey,Anosim,and metastats analysis were used to compare differences of microbiota among different groups.Results:After gavage for 1 week,the pathologic scores of groups with the intervention were significantly lower than those in the model control group,and the difference was statistically significant (P < 0.05).The model control group was higher in the genus of Bacteroides (relative abundance:0.3679 vs.0.0099,P =0.0016) and lower in Lactobacillus (relative abundance:0.0020 vs.0.0122,P =0.0188),Roseburia (relative abundance:0.0004 vs.0.0109,P =0.0157),compared with the blank control group.However,the same phenomenon was not found in groups gavaged with probiotics and lactitol.Compared with model control group,mice with intervention were increased with Bifidobacterium (relative abundance:0.0172 vs.0.0039,P =0.0139),Lachnospiraceae_NK4A136_group (relative abundance:0.1139 vs.0.0320,P =0.0344),Lachnospiraceae_UCG-006 (relative abundance:0.0432 vs.0.0054,P =0.0454),and decreased with Alistipes (relative abundance:0.0036 vs.0.0105,P =0.0207) in varying degrees.The mucosal flora was more abundant than the fecal flora,and genus of Mucispirillum (relative abundance:0.0207 vs.0.0001,P =0.0034) was more common in the mucosa.Lactitol group showed higher level of Akkermansia than model control group (relative abundance:0.0138 vs.0.0055,P =0.0415),probiotics group (relative abundance:0.0138 vs.0.0022,P =0.0041),and synbiotics group (relative abundance:0.0138 vs.0.0011,P =0.0034),while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance:0.0215 vs.0.0013,P =0.0315).Conclusions:Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously.Mice with acute colitis show reduced beneficial genera and increased harmful genera.Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota.Lactitol might promote the proliferation of Akkermansia.

Preoperative Corticosteroid Usage and Hypoalbuminemia Increase Occurrence of Short-term Postoperative Complications in Chinese Patients with Ulcerative Colitis

Background： Clarifying the risk factors for postoperative complications and taking measures to minimize these complications will improve the outcomes in patients with ulcerative colitis （UC）.This study aimed to systemically explore the risk factors for short-term postoperative complications in Chinese UC patients undergoing ileocolorectal surgery.Methods： Forty-nine UC patients undergoing proctocolectomy or ileostomy were retrospectively enrolled.Univariate and multivariate logistic regression analyses were conducted to reveal the risk factors among the clinical, laboratory, and surgical variables as well as preoperative medications.Results： Twenty-two （44.9%） patients who suffered from at least one short-term postoperative event had more severe hypoalbuminemia （P =0.007） and an increased prevalence of preoperative corticosteroid usage （prednisone more than 20 mg daily or equivalent） for more than 6 weeks （59.1% vs.25.9%, P =0.023） compared with patients without short-term postoperative complications.Based on the multivariate logistic regression analysis, the odds ratio （95% confidence interval） values of these two risk factors were 1.756 （0.889-3.470, P =0.105） and 3.233 （0.916-11.406, P =0.068）, respectively.In 32 severe UC patients, prolonged preoperative hospital stay worsened the short-term postoperative outcomes.Conclusions： Preoperative corticosteroids usage and hypoalbuminemia worsened the short-term outcomes following ileocolorectal surgery in Chinese UC patients.

Discriminating Potential of Extraintestinal Systemic Manifestations and Colonoscopic Features in Chinese Patients with Intestinal Beh~：et＇s Disease and Crohn＇s Disease

Background：The distinction between intestinal Beh（c）et＆#39;s disease （BD） and Crohn＆#39;s disease （CD） is always challenging due to many overlapping clinical features.We conducted a retrospective study to reveal valuable strategies for the differential diagnosis between intestinal BD and CD in Chinese patients based on their clinical and colonoscopic features.Methods：Thirty-five intestinal BD patients and 106 CD patients hospitalized from January 1983 to January 2010,who had ulcerative lesions in the terminal ileum or colon under colonoscopy and no history of gastrointestinal operation except appendectomy before admission,were enrolled.Univariate and multivariate logistic regression analyses were conducted to find discriminating predictors among demographic data,clinical manifestations,and colonoscopic findings.Results：Based on univariate analysis,massive gastrointestinal hemorrhage,fever,and extraintestinal systemic manifestations were more common in intestinal BD patients （P =0.022,0.048 and 0.001,respectively）,while diarrhea,intestinal obstruction,and perianal lesions were more common in CD patients （P =0.002,0.010,and 0.027 respectively）.Based on colonoscopy,focal involvement,ileocecal valve deformity,solitary ulcers,large ulcers （ulcer size 〉 2 cm）,and circumferential ulcers were more common in intestinal BD patients （P =0.003,0.003,0.014,0,013,and 0.003,respectively）,while segmental involvement,longitudinal ulcers,a cobblestone or nodular appearance,and pseudo-polyps were more common in CD patients （P =0.003,0.008,0.023,and 0.002,respectively）.Based on multivariate logistic regression analysis,diarrhea,extraintestinal manifestations,ulcer distribution,size,and type,and pseudo-polyps were independent discriminating predictors between the two groups （P =0.048,0.008,0.006,0.021,0.002,and 0.041,respectively）.The discriminating algorithm composed of the above independent predictors had the highest area under the curve of 0.987 for distinguishing between the two diseases.Conclusions：Extraintestinal systemic manifestations and the characteristic colonoscopic features,such as ulcer distribution,size and type,helped to distinguish intestinal BD from CD.

Artificial intelligence in inflammatory bowel disease:current status and opportunities

In the past decade,artificial intelligence(Al)has been applied in several clinical studies to improve the medical care of patients with gastroenterological diseases,to accurately detect polyps and early cancer lesions,to facilitate the analysis of inflammatory lesions,to assess liver fibrosis,and to predict the response and clinical outcomes of medications.[1-2]Inflammatory bowel disease(IBD),comprising Crohn disease(CD)and ulcerative colitis(UC),is a prototypical complex disease that has been considered a significant healthcare burden in the healthcare system of Western countries.

Polyp recurrence after colonoscopic polypectomy

Colorectal cancer(CRC)is the third most commonly diagnosed malignant tumor in the world.The past few years have seen a remarkable increase in both incidence and mortality of CRC in developing countries like China,posing a serious threat to human health.It is currently believed that about 70%of colorectal cancers are derived from conventional adenomas and 30%are derived from serrated adenomas.[1]As reported,CRC incidence rates per 10,000 person-years were 20.0 for advanced adenoma and 9.1 for non-advanced adenoma.[2]Colonoscopy,as an important tool for CRC screening and follow-up,can prevent the development of CRC by detecting and removing precancerous lesions,thereby effectively reducing the incidence and mortality.Current guidelines for post-polypectomy surveillance mostly recommend a 3-to 10-year interval according to baseline risk stratification.[3]However,there is no such guideline in China yet and doctors tend to perform the next colonoscopy within 1 year,which is much shorter than current international recommendations.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada

Background:Colorectal cancer(CRC)has become one of the major life-threatening complications in patients with inflammatory bowel disease(IBD),which includes ulcerative colitis(UC)and Crohn's disease(CD).This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associ吐ed CRC(IBD-CRC)between patients in China and Canada.Methods:Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing(China)and Calgary(Canada)over the same past 13 years,including 25(22 UC-associated and three CD-associated)from Beijing group and 53(32 UC-associated and 21 CD-associated)from Calgary group,were compared with regards to their clinical and pathologic characteristics.Results:Several known features of IBD-CRC were seen in both groups,including long duration and large extent of colitis,active inflammation background,multifocal lesions,and advanced tumor-node-metastasis stage.Beijing group showed a significantly higher percentage of UC(88.0%vs.60.4%,P=0.018),younger age at diagnosis of CRC(48.6±12.8 years vs.61.6±14.7 years,P<0.001),lower ratio of mucinous adenocarcinoma(7.1%us.42.4%,P=0.001)compared with Calgary group.None of the Beijing group had concurrent primary sclerosing cholangitis,while 5.7%of Calgary group did.Surveillance colonoscopy favored the detection rate of precancerous lesions(41.4%vs.17.0%,P=0.002).Conclusions:As compared with patients from the Calgary group,the IBD-CRC patients in Beijing group were younger,less CDassociated and had less mucinous features,otherwise they were similar in many common features.

Comparison of Clinical Features between Pyoderma Gangrenosum Concomitant by Inflammatory Bowel Disease and Idiopathic Pyoderma Gangrenosum

Background： Pyoderma gangrenosum （PG） is a rare neutrophilic dermatosis that is highly associated with inflammatory bowel disease （IBD）. Certain PG patients with no systemic disorders have been diagnosed with idiopathic PG. This study sought to clarity/the difference between PG with IBD and idiopathic PG based on clinical features, laboratory tests, and medications. Methods： Twelve patients with PG and IBD and 24 patients with idiopathic PG, who were hospitalized in Peking Union Medical College Hospital from 2000 to 2017, were retrospectively categorized into the IBD group and control group, respectively. Data of clinical features, laboratory tests, and medications were collected and compared between the two groups. Results： Both groups were similar with respect to their clinical features. However, the IBD group had an increased occurrence of arthralgia or arthritis （58.3% vs. 12.5%, P = 0.007）, anemia （83.3% and 29.2%, P = 0.004）, and an increased percentage ofantineutrophilic cytoplasmic antibody （ANCA）-positive patients （85.7% and 0.0%, P 〈 0.001）, compared to the control group. Conclusion： PG patients with IBD had increased occurrence rates of arthralgia or arthritis, anemia, and ANCA-positive status compared to idiopathic PG patients.

Cronkhite-Canada syndrome complicated with three malignant tumors: a case report and whole exome sequencing analysis

To the Editor:Cronkhite-Canada syndrome(CCS)is a rare,non-hereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities.[1]Although CCS polyps are not considered to be neoplastic,15%to 25%patients have been documented with colorectal or gastric cancer at diagnosis,and up to 40%of patients have been documented with adenomas and adenomatous changes.[2]Extra-gastrointestinal neoplasms have been sporadically reported,but their association with CCS remains under investigation.The underlying mechanism of CCS has been less investigated,with only one whole exome sequencing(WES)study that identified a protein kinase DNA-activated catalytic subunit(PRKDC)DNA variant that might contribute to the pathogenesis.[3]Here,we report a case of CCS that was complicated with three malignant tumors.WES analysis of this case identified certain germline mutations that might provide insight into the pathogenesis.This study was approved by the Ethics Committee of Peking Union Medical College Hospital,Peking Union Medical College and Chinese Academy of Medical Sciences(No.ZS-1725).

Enteral fistula as initial manifestation of primary intestinal lymphoma

To the Editor:Enteral fistula(EF)is a rare complication mostly caused by inflammatory bowel disease and in some cases by duodenal ulcer,intestinal tuberculosis,intestinal lymphoma,abdominal surgery,or necrotizing enterocolitis.[1,2]Perforative complications including perforation and EF are major complications of primary intestinal lymphoma(PIL).Vaidya et al[2]reported that in a cohort of 1062 patients with gastrointestinal lymphoma,bowel perforation occurred in 9%of the patients,and among them,the small intestine was the most common site(81%).Furthermore,perforation events occurred as the initial presentation in 51%of these patients.

Corrigendum to:Association between matrix Gla protein and ulcerative colitis according to DNA microarray data

In the original version of this manuscript the author’s affiliation was incorrect.This has been corrected to:Department of Gastroenterology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,P.R.China.