BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to th...BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.展开更多
Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as ...Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.展开更多
BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CA...BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CASE SUMMARY A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture.Abdominal ultrasound showed a bright liver,and laboratory investigations revealed low lowdensity lipoprotein cholesterol and apolipoprotein B protein levels.His family history included fatty liver and hypolipidemia in his father,which led to a clinical diagnosis of FHBL.A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers.The liver tissue showed fatty steatosis,inflammation,hepatocyte ballooning,and fibrosis,indicating NASH.Genetic testing detected the APOB variant,and the patient was treated successfully with vitamin E.CONCLUSION It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver.展开更多
Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over...Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over 20%in the elderly(Yamada et al.,2013),yet the underlying mechanisms of brain calcification remain poorly understood.Specifically,calcification in the basal ganglia is detected in approximately 5.5%-20%of CT scans in patients over 50 years old(Auffray-Calvier et al.,2020).展开更多
BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenes...BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of ...BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of adenomas in the colon during the second decade of life.If prophylactic colectomy is not performed,most patients eventually develop colorectal cancer(CRC).CASE SUMMARY We present the mutational profile of a case of FAP that progressed to CRC.A 45-year-old Saudi man presented with intestinal obstruction and underwent a total colectomy.The colon showed hundreds of polyps and two infiltrative ulcerative lesions,which proved to be adenocarcinoma according to histopathology.We performed next-generation sequencing and found mutations in the TP53,NRAS,EGFR PDGFR,MET,KIT,ERBB2,and GUSP genes.CONCLUSION To the best of our knowledge,this case report is the first to sheds the light on the mutation profile of FAP that progressed to CRC in Saudi Arabia.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recom...BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.展开更多
This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasize...This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.展开更多
Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and ...Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and progressive liver disease.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.The impaired bile flow within the liver,leads to accumulation in the liver and inflammation.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion,with an aim to interrupt the enterohepatic circulation.These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids,reducing pruritus and liver injury and improving the patient quality of life.Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter(IBAT).IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus.We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.展开更多
This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patient...This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system whi...Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.展开更多
AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in bo...AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in both familial and non-familial primary open angle glaucoma(POAG)patients.METHODS:A total of 212 POAG patients,comprising 124 familial and 88 non-familial,were enrolled.For genotyping the SMOC2 variant rs2255680,amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)method and PCR-restriction fragment length polymorphism(PCR-RFLP)were utilized for analyzing rs13208776 variant.RESULTS:The mean age of familial POAG patients was 50.92±9.12y,with 78 males and 46 females.The mean age of non-familial POAG patients was 53.14±13.44y,with 52 males and 36 females.The SMOC2 gene variant rs13208776 showed the significant association with POAG between familial and non-familial groups.The homozygous G/G variant was frequent among non-familial(60.2%)whereas the heterozygous G/A variant was more frequent in familial POAG patients(46%).There were significant differences in G/A variant between familial and non-familial glaucoma patients,and the risk was decreased to 0.53-fold in non-familial glaucoma patients[odds ratio(OR):0.53;95%confidence interval(CI):0.29-0.94;P=0.033]in codominant model.The risk was further reduced to 0.49-fold(95%CI:0.28-0.86;P=0.012)in dominant model for non-familial patients.No significant association of SMOC2 gene variant rs2255680 between familial and non-familial glaucoma patients was found in our population.The haplotype analysis showed the decreased risk for TA[OR:0.48(95%CI:0.29-0.79);P=0.004]and an increased risk for TG[OR=2.28(95%CI:1.22-4.25);P=0.01]haplotypes.CONCLUSION:Current findings show significant association of SMOC2 gene variant rs13208776 with POAG between familial and non-familial Pakistani patients.展开更多
In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family his...In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.展开更多
Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performe...Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase ...AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.展开更多
BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on'progressive familial intrahepatic ...BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on'progressive familial intrahepatic cholestasis'and'PFIC'was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.展开更多
Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis...Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.展开更多
Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch ha...Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.展开更多
基金Supported by the Research Grants of the National Research,Development and Innovation Office,No.K125377,No.K134863 and No.K143549New National Excellence Program of the Ministry of Human Capacities,No.UNKP-20-5-SZTE-161,No.UNKP-22-3-SZTE-233,No.UNKP-23-5-SZTE-719,No.UNKP-22-4-SZTE-296 and No.UNKP-22-3-SZTE-278+1 种基金Janos Bolyai Research Grant,No.BO/00723/22the Géza Hetényi Research Grant by Albert Szent-Györgyi Medical School,University of Szeged.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is a disorder of autosomal dominant inheritance that is responsible for around 1%of colorectal cancer(CRC)cases.AIM To determine the mutation profile of FAP-specific to the Hungarian population.METHODS This prospective single-center study enrolled patients with clinically suspected FAP or attenuated FAP(aFAP).Whole-exome next-generation sequencing was performed to detect variants of 50 FAP priority genes and 173 CRC predisposing genes or other CRC disease-associated genes.To identify larger deletions and insertions,a multiplex amplifiable probe hybridization technique was used.The identified genes were then classified according to the American College of Medical Genetics and Genomics guidelines.RESULTS A total of 26 index patients with clinically suspected FAP(n=21)and aFAP(n=5)were enrolled.APC gene alterations were confirmed in 92.31%of the cases(region 1B deletion,n=2;whole-gene deletion,n=4;frameshift mutation,n=2;nonsense mutation,n=5,and splice mutation,n=1),with the remaining two cases having CHEK2 and MSH3 gene alterations.According to pathogenicity,21 cases had pathogenic mutations,6 cases had likely pathogenic mutations,and 16 cases had variants of unknown significance(VUS).The most frequent of the latter were the POLE(n=5)and PIEZO1(n=4)gene variants.CONCLUSION Germline mutations in the APC gene were confirmed in more than 90%of Hungarian patients with clinically suspected FAP.Although the role of VUS genes is unclear,they are highly likely to play a role in the development of CRC.
文摘Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.
文摘BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CASE SUMMARY A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture.Abdominal ultrasound showed a bright liver,and laboratory investigations revealed low lowdensity lipoprotein cholesterol and apolipoprotein B protein levels.His family history included fatty liver and hypolipidemia in his father,which led to a clinical diagnosis of FHBL.A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers.The liver tissue showed fatty steatosis,inflammation,hepatocyte ballooning,and fibrosis,indicating NASH.Genetic testing detected the APOB variant,and the patient was treated successfully with vitamin E.CONCLUSION It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver.
基金supported by the Natural Science Foundation of China(32270663 and 31230045 to J.Y.L.)China Postdoctoral Science Foundation(2024M762007 and GZB20240453 to J.L.)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05 to J.Y.L.).
文摘Brain calcification is frequently detected by neuroimaging in patients with hereditary and nonhereditary disorders or in normal individuals with aging.Its prevalence ranges from approximately 1%in young people to over 20%in the elderly(Yamada et al.,2013),yet the underlying mechanisms of brain calcification remain poorly understood.Specifically,calcification in the basal ganglia is detected in approximately 5.5%-20%of CT scans in patients over 50 years old(Auffray-Calvier et al.,2020).
文摘BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of adenomas in the colon during the second decade of life.If prophylactic colectomy is not performed,most patients eventually develop colorectal cancer(CRC).CASE SUMMARY We present the mutational profile of a case of FAP that progressed to CRC.A 45-year-old Saudi man presented with intestinal obstruction and underwent a total colectomy.The colon showed hundreds of polyps and two infiltrative ulcerative lesions,which proved to be adenocarcinoma according to histopathology.We performed next-generation sequencing and found mutations in the TP53,NRAS,EGFR PDGFR,MET,KIT,ERBB2,and GUSP genes.CONCLUSION To the best of our knowledge,this case report is the first to sheds the light on the mutation profile of FAP that progressed to CRC in Saudi Arabia.
基金Supported by the National Natural Science Foundation of China,No.82471804.
文摘BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.
文摘This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.
文摘Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and progressive liver disease.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.The impaired bile flow within the liver,leads to accumulation in the liver and inflammation.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion,with an aim to interrupt the enterohepatic circulation.These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids,reducing pruritus and liver injury and improving the patient quality of life.Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter(IBAT).IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus.We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.
基金National Natural Science Foundation of China,No.82370569Basic and Applied Basic Research Foundation of Guangdong Province,No.2022A1515012647the Key Program for Science and Technology Projects of Social Development in Zhuhai,No.2220004000249(to Li XF).
文摘This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
基金Supported by Grants from Ministerio de Ciencia e Innovación(SAF2008/03676) and Fundació Miarnau to Sans M
文摘Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.
基金Supported by Higher Education Commission of Pakistan(NRPU#2835)Pakistan Science Foundation Project No.Biotech 101,funded to Professor Dr.Ali Muhammad Waryah.
文摘AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in both familial and non-familial primary open angle glaucoma(POAG)patients.METHODS:A total of 212 POAG patients,comprising 124 familial and 88 non-familial,were enrolled.For genotyping the SMOC2 variant rs2255680,amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)method and PCR-restriction fragment length polymorphism(PCR-RFLP)were utilized for analyzing rs13208776 variant.RESULTS:The mean age of familial POAG patients was 50.92±9.12y,with 78 males and 46 females.The mean age of non-familial POAG patients was 53.14±13.44y,with 52 males and 36 females.The SMOC2 gene variant rs13208776 showed the significant association with POAG between familial and non-familial groups.The homozygous G/G variant was frequent among non-familial(60.2%)whereas the heterozygous G/A variant was more frequent in familial POAG patients(46%).There were significant differences in G/A variant between familial and non-familial glaucoma patients,and the risk was decreased to 0.53-fold in non-familial glaucoma patients[odds ratio(OR):0.53;95%confidence interval(CI):0.29-0.94;P=0.033]in codominant model.The risk was further reduced to 0.49-fold(95%CI:0.28-0.86;P=0.012)in dominant model for non-familial patients.No significant association of SMOC2 gene variant rs2255680 between familial and non-familial glaucoma patients was found in our population.The haplotype analysis showed the decreased risk for TA[OR:0.48(95%CI:0.29-0.79);P=0.004]and an increased risk for TG[OR=2.28(95%CI:1.22-4.25);P=0.01]haplotypes.CONCLUSION:Current findings show significant association of SMOC2 gene variant rs13208776 with POAG between familial and non-familial Pakistani patients.
文摘In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.
文摘Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
基金Supported by The National Natural Science Foundation of China,No.30940086
文摘AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.
文摘BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on'progressive familial intrahepatic cholestasis'and'PFIC'was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.
文摘Familial pancreatic cancer(FPC)is broadly defined as two first-degree-relatives with pancreatic cancer(PC)and accounts for 4%-10%of PC.Several genetic syndromes,including Peutz-Jeghers syndrome,hereditary pancreatitis,hereditary breast-ovarian cancer syndrome(HBOC),Lynch syndrome,and familial adenomatous polyposis(FAP),also have increased risks of PC,but the narrowest definition of FPC excludes these known syndromes.When compared with other familial tumors,proven genetic alterations are limited to a small proportion(<20%)and the familial aggregation is usually modest.However,an ethnic deviation(Ashkenazi Jewish>Caucasian)and a younger onset are common also in FPC.In European countries,"anticipation"is reported in FPC families,as with other hereditary syndromes;a trend toward younger age and worse prognosis is recognized in the late years.The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia(Pan IN)foci,with various K-ras mutations,similar to colorectal polyposis seen in the FAP patients.As with HBOC patients,a patient who is a BRCA mutation carrier with unresectable pancreatic cancer(accounting for 0%-19%of FPC patients)demonstrated better outcome following platinum and Poly(ADP-ribose)polymerase inhibitor treatment.Western countries have established FPC registries since the 1990 s and several surveillance projects for highrisk individuals are now ongoing to detect early PCs.Improvement in lifestyle habits,including non-smoking,is recommended for individuals at risk.In Japan,the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.
文摘Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.
