Hsa_circ_0036740 in familial adenomatous polyposis:Immune regulation and neutrophil effects in CRC based on highthroughput assay

Familial adenomatous polyposis(FAP)is an autosomal dominant disease with a high probability of becoming cancerous.Many RNAs potentially associated with FAP have not been identified.In this study,a circRNA(circular RNA)expression profile of FAP was established using a circRNA microarray,and differentially expressed circRNAs were verified by RT-qPCR.The effects of hsa_circ_0036740 on the malignant behavior of tumor cells(proliferation,apoptosis,and epithelial mesenchymal transition)and the levels of C3A complement protein expression were evaluated.Moreover,neutrophils were isolated and co-cultured with colorectal cancer cells(CRCs),followed by measurements of MPO-DNA,citrullinated histone H3,interleukin(IL)-1β,IL-6,and IL-8 levels.Nuclear translocation of arginine deiminase 4(PAD4)was observed using immunofluorescence assays.Based on the high-throughput assay,238 downregulated circRNAs,and 38 upregulated circRNAs were identified.A Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that immune regulation might be involved in FAP.A total of 10 DECs(differentially expressed circular RNAs)were identified by RT-qPCR,and among them,hsa_circ_0036740 showed the highest fold-change in upregulation.Results of gain-of-and loss-of-function studies revealed that hsa_circ_0036740 enhanced the malignant behavior of tumor cells,such as metastasis,proliferation,and apoptosis,with an increasing level of C3A complement.Moreover,hsa_circ_0036740 also significantly increased neutrophil extracellular trap formation and inflammation in neutrophils,as shown by an increased expression of PAD4.In conclusion,this study revealed the expression profiles of circRNAs in FAP and confirmed the possible involvement of hsa_circ_0036740 in the immune regulation mediated by neutrophils.Finally,hsa_circ_0036740 was suggested as a new therapeutic target for CRC.

APC gene mutations in Chinese familial adenomatous polyposis patients

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.

Surgical treatment of familial adenomatous polyposis: Dilemmas and current recommendations

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps (predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient’s preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.

Familial adenomatous polyposis and changes in the gut microbiota: New insights into colorectal cancer carcinogenesis

Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer.Some gut bacteria,such as Fusobacterium nucleatum,Escherichia coli,Clostridium difficile,Peptostreptococcus,and enterotoxigenic Bacteroides fragilis,could be implicated in colorectal carcinogenesis through different mechanisms,including the maintenance of a chronic inflammatory state,production of bioactive tumorigenic metabolites,and DNA damage.Studies using the adenomatous polyposis coliMin/+mouse model,which resembles FAP in most respects,have shown that specific changes in the intestinal microbial community could influence a multistep progression,the intestinal“adenoma-carcinoma sequence”,which involves mucosal barrier injury,low-grade inflammation,activation of the Wnt pathway.Therefore,modulation of gut microbiota might represent a novel therapeutic target for patients with FAP.Administration of probiotics,prebiotics,antibiotics,and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP.The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.

Wireless capsule endoscopy in detecting small-intestinal polyps in familial adenomatous polyposis

AIM:To detect the prevalence of small bowel polyps by wireless capsule endoscopy(WCE)in patients with familial adenomatous polyposis(FAP).METHODS:We examined prospectively 14 patients with FAP to assess the location,size and number of small-intestinal polyps.Patients'age,sex,years of observation after surgery,type of surgery,duodenal polyps and colorectal cancer at surgery were analyzed.RESULTS:During WCE,polyps were detected in 9/14(64.3%)patients.Duodenal adenomatous polyps were found in nine(64.3%)patients,and jejunal and ileal polyps in seven(50%)and eight(57.1%),respectively.The Spigelman stage of duodenal polyposis was associated with the presence of jejunal and ileal polyps.Identification of the ampulla of Vater was not achieved with WCE.Importantly,the findings of WCE had no immediate impact on the further clinical management of FAP patients.No procedure-related complications were observed in the patients.CONCLUSION:WCE is a promising noninvasive new method for the detection of small-intestinal polyps.Further investigation is required to determine which phenotype of FAP is needed for surveillance with WCE.

Rare combination of familial adenomatous polyposis and gallbladder polyps

Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.

Presence of c.3956del C mutation in familial adenomatous polyposis patients from Brazil

AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros Barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose in one member belonging to this state from Brazil). CONCLUSION: Regardless of its origin,the c.3956 del C mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.

Duodenal adenoma surveillance in patients with familial adenomatous polyposis

Familial adenomatous polyposis(FAP) is a hereditary disorder caused by Adenomatous Polyposis Gene mutations that lead to the development of colorectal polyps with great malignant risk throughout life. Moreover, numerous extracolonic manifestations incorporate different clinical features to produce varied individual phenotypes. Among them, the occurrence of duodenal adenomatous polyps is considered an almost inevitable event, and their incidence rates increase as a patient's age advances. Although the majority of patients exhibit different grades of duodenal adenomatosis as they age, only a small proportion(1%-5%) of patients will ultimately develop duodenal carcinoma. Within this context, the aim of the present study was to review the data regarding the epidemiology, classification, genetic features, endoscopic features, carcinogenesis, surveillance and management of duodenal polyps in patients with FAP.

Adenocarcinomas after Prophylactic Surgery for Familial Adenomatous Polyposis

The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch;however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers;15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.

Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis markers.METHODS: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni’s test, and Pearson’s correlation test were applied for statistical analysis.RESULTS: ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson’s correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic tissue.CONCLUSION: This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER-α showed the opposite trend. ER-β/caspase 3 co-expression suggests this hormone’s possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach.

Cumulative incidence and risk factors for pouch adenomas associated with familial adenomatous polyposis following restorative proctocolectomy

BACKGROUND The emergence of restorative total proctocolectomy has significantly reduced the lifetime colorectal cancer risk associated with familial adenomatous polyposis(FAP).However,adenomas may develop in the ileal pouch over time and may even progress to carcinoma.We evaluated the cumulative incidence,time to development,and risk factors associated with ileal pouch adenoma.AIM To evaluate the cumulative incidence,time to development,and risk factors associated with pouch adenoma.METHODS In this retrospective,observational study conducted at a tertiary center,95 patients with FAP who underwent restorative proctocolectomy at our center between 1989 and 2018 were consecutively included.The mean follow-up period was 88 mo.RESULTS Pouch adenomas were found in 24(25.3%)patients,with a median time of 52 mo to their first formation.Tubular adenomas were detected in most patients(95.9%).There were no high-grade dysplasia or malignancies.Of the 24 patients with pouch adenomas,13 had all detected adenomas removed.Among the 13 patients who underwent complete adenoma removal,four(38.5%)developed recurrence.Among 11(45.8%)patients with numerous polyps within the pouch,seven(63.6%)exhibited progression of pouch adenoma.The cumulative risks of pouch adenoma development at 5,10,and 15 years after pouch surgery were 15.2%,29.6%,and 44.1%,respectively.Severe colorectal polyposis(with more than 1000 polyps)was a significant risk factor for pouch adenoma development(hazard ratio,2.49;95% confidence interval:1.04-5.96;P=0.041).CONCLUSION Pouch adenomas occur at a fairly high rate in association with FAP after restorative proctocolectomy,and a high colorectal polyp count is associated with pouch adenoma development.

Three Novel Mutations of APC Gene Found in a Chinese Family with Familial Adenomatous Polyposis

Objective:To identify the causative adenomatous polyposis coli(APC)gene defects associated with a pedigree of familial adenomatous polyposis(FAP).Methods:FAP was diagnosed based on clinical manifestations,family history,as well as endoscopic and pathological examinations.The blood samples of the FAP pedigree members,colonic polyp patients,and normal individuals were collected.Genomic DNA was then extracted from those samples.APC mutation analysis was conducted via direct polymerase chain reaction(PCR)sequencing.Results:Three synonymous mutations and a missense mutation were found:c.5034G>A(p.Glyl678Gly),c.5465T>A(p.Vall 822Asp),c.5880G>A(p.Prol960Pro),and c.5274T>G(p.Serl758Ser)・Among them,the homozygous mutation on APC gene c.5034G>A has been reported,while the other three mutations have not been reported in the Chinese Han population.Individuals with c.5465T>A(p.Vall822ASP)missense mutation eventually suffer from colon cancer and have poor prognosis.We found no mutation in patients with simple intestinal polyp and in normal individuals.In addition,there were homozygous and heterozygous mutations in different patients from the same family.Conclusion:Three new mutations of APC gene were firstly reported in Han population.The missense mutation of c.5465T>A(p.Vall 822Asp)may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.

Attenuated adenomatous polyposis of the large bowel: Present and future

Attenuated adenomatous polyposis(AAP) is a poorly understood syndrome, that can be defined as the presence of 10-99 synchronous adenomas in the large bowel, and it is considered a phenotypic variant of familial adenomatous polyposis(FAP). This definition has the advantage of simplicity, but it may include sporadic multiple adenomas of the large bowel at an extreme, or FAP cases on the other side. AAP shows a milder phenotype than FAP, with an older age of onset of adenomas and cancer, and less frequent extracolonic manifestations. AAP may be diagnosed as a single case in a family or, less frequently, it may be present in other family members, and it shows distinct pattern of inheritance. In less than 50% of cases, it may be caused by adenomatous polyposis coli(APC) or MUTYH mutations, referred to as APC-associated polyposis, inherited as an autosomal dominant trait, or MUTYH-associated polyposis, which shows an autosomal recessive mechanism of inheritance, respectively. Surveillance should rely on colonoscopy at regular intervals, with removal of adenomas and careful histological examination. When removal of polyps is not possible or advanced lesions are observed, the surgical approach is mandatory, being subtotal colectomy with ileo-rectal anastomosis the treatment of choice. Studies on this syndrome are lacking, and controversies are still present on many issues, thus, other clinical and genetic studies are requested.

Hereditary polyposis syndromes remain a challenging disease entity:Old dilemmas and new insights

In this editorial we present an overview and insights of the management of hereditary polyposis syndromes.The primary focus was on familial adenomatous polyposis,juvenile polyposis syndrome and Peutz-Jegher syndrome.Genetic testing has become increasingly available and is easier than ever to integrate into clinical practice.Furthermore,several genes have been added to the expanding list of genes associated with hereditary polyposis syndromes,allowing for precise diagnostics and tailored follow-up.Endoscopic evaluation of patients with hereditary polyposis syndromes is paramount in the surveillance strategies.Current endoscopic procedures include both diagnostic procedures and surveillance as well as therapeutic interventions.Recommendations for endoscopic procedures in the upper and lower gastrointestinal canal were described.Surgery is still a key component in the management of patients with hereditary polyposis syndromes.The increased cancer risk in these patients often render prophylactic procedures or intended curative procedures in the case of cancer development.Surgical interventions in the upper and lower gastrointestinal canal were described with relevant considerations.Development of chemopreventive medications is ongoing.Few drugs have been investigated,including nonsteroidal anti-inflammatory drugs.It has been demonstrated that cyclooxygenase-2 inhibitors may lower the number of polyps.Other medications are currently under investigation,but none have,to date,consistently been able to prevent development of disease.

Management of pouch related symptoms in patients who underwent ileal pouch anal anastomosis surgery for adenomatous polyposis

BACKGROUND Adenomatous polyposis syndromes(APS)patients with ileal pouch anal anastomosis(IPAA)suffer frequent symptoms with scarce signs of inflammation,distinct from ulcerative colitis patients.While the management of pouchitis in ulcerative colitis patients is well established,data regarding response to treatment modalities targeting pouch-related disorders in APS patient population is scarce.AIM To assess clinical,endoscopic and histologic response to various treatment modalities employed in the therapy of pouch related disorders.METHODS APS patients who underwent IPAA between 1987-2019 were followed every 6-12 mo and pouch-related symptoms were recorded at every visit.Lower endoscopy was performed annually,recording features of the pouch,cuff and terminal ileum.A dedicated gastrointestinal pathologist reviewed biopsies for signs and severity of inflammation.At current study,files were retrospectively reviewed for initiation and response to various treatment modalities between 2015-2019.Therapies included dietary modifications,probiotics,loperamide,antibiotics,bismuth subsalicylate,mebeverine hydrochloride,5-aminosalicylic acid compounds and topical rectal steroids.Symptoms and endoscopic and histologic signs of inflammation before and after treatment were assessed.Pouchitis disease activity index(PDAI)and its subscores was calculated.Change of variables before and after therapy was assessed using Wilcoxon signed rank test for continuous variables and using McNemar's test for categorical variables.RESULTS Thirty-three APS patients after IPAA were identified.Before treatment,16 patients(48.4%)suffered from abdominal pain and 3(9.1%)from bloody stools.Mean number of daily bowel movement was 10.3.Only 4 patients(12.1%)had a PDAI≥7.Mean baseline PDAI was 2.5±2.3.Overall,intervention was associated with symptomatic relief,mainly decreasing abdominal pain(from 48.4%to 27.2%of patients,P=0.016).Daily bowel movements decreased from a mean of 10.3 to 9.3(P=0.003).Mean overall and clinical PDAI scores decreased from 2.58 to 1.94(P=0.016)and from 1.3 to 0.87(P=0.004),respectively.Analyzing each treatment modality separately,we observed that dietary modifications decreased abdominal pain(from 41.9%of patients to 19.35%,P=0.016),daily bowel movements(from 10.5 to 9.3,P=0.003),overall PDAI(from 2.46 to 2.03,P=0.04)and clinical PDAI(1.33 to 0.86,P=0.004).Probiotics effectively decreased daily bowel movements(from 10.2 to 8.8,P=0.007),overall and clinical PDAI(from 2.9 to 2.1 and from 1.38 to 0.8,P=0.032 and 0.01,respectively).While other therapies had minimal or no effects.No significant changes in endoscopic or histologic scores were seen with any therapy.CONCLUSION APS patients benefit from dietary modifications and probiotics that improve their pouch-related symptoms but respond minimally to anti-inflammatory and antibiotic treatments.These results suggest a functional rather than inflammatory disorder.

Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

Diagnosis and treatment of Gardner syndrome with gastric polyposis: A case report and review of the literature

Gardner syndrome (GS) is an autosomal dominant disease characterized by the presence of colonic polyposis, osteoma and soft tissue tumors. It is regarded as a clinical subgroup of familial adenomatous polyposis (FAP) and may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 23-year-old female patient with GS who presented with gastric polyposis and was successively treated with restorative proctocolectomy in combination with ileal pouch anal anastomosis (RPC/ IPAA), ileostomy, ileostomy closure operation, snare polypectomy during 8 mo. After operation, the patient took oral traditional Chinese medicine pills made of Fructus mume and Bombyx batryticatu for about 6 mo. The innutrition and anaemia of this patient were gradually improved. Gastroscopy showed that the remnant gastric polypi gradually decreased and finally disappeared 19 mo after the first operation. The patient had 2-3 times of solid stool per day at the time we wrote this paper.

Absence of MutY homologue mutation in patients with multiple sporadic adenomatous polyps in Korea

AIM： Recently, germ-line mutation in the base excision repair gene MYH has been identified to cause a novel autosomal recessive form of familial adenomatous polyposis （FAP）. Interestingly, a striking evidence for MYH mutations within different ethnic groups has been demonstrated. In this study, we screened 30 patients with multiple adenomatous polyps for MYH mutations to assess its prevalence and ethnic specificity in Korea. METHODS： Thirty patients （21 men and 9 women; mean age 62.3 years） with multiple adenomatous polyps were examined for MYH mutations. The mean number of adenomas per patient was 10.0. Sixteen exonic regions and their intronic sequences were amplified by PCR and subjected to SSCP and DNA sequencing analyses. RESULTS： None of the patients was identified to carry any truncating or sequence alterations in MYH. Our screening for the mutational regions, which were recognized from Caucasian patients or affected Indian families, also failed to detect sequence substitutions. CONCLUSION： Mutation in MYHmay be rarely involved in the pathogenesis of multiple sporadic colorectal adenomas in Korean population, although a large-scale analysis will be required to clarify the presence of specific MYH variants in a subset of patients and their role in the predisposition of multiple colorectal adenomas in Korean population.

Gardner's syndrome:Genetic testing and colonoscopy are indicated in adolescents and young adults with cranial osteomas:A case report

We present a case of a 25-year-old female with diagnosed familial adenomatous polyposis and elevated carcinoembryonic antigen with negative family history. The suspicion of Gardner's syndrome was raised because extirpation of an osteoma of the left temporo-occipital region was made 10 years ago. Restorative procto-colectomy and ileal pouch anal anastomosis was made but histology delineated adenocarcinoma of the rectum (Dukes C stage). We conclude that cranial osteomas often precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome and such patients should be evaluated with genetic testing followed by colonoscopy if results are positive to prevent the development of colorectal carcinoma. If the diagnosis is positive all family members should be evaluated for familial adenomatous polyposis.

Anorectal functional outcome after repeated transanal endoscopic microsurgery

AIM： TO evaluate the status of anorectal function after repeated transanal endoscopic microsurgery （TEN）. METHODS： Twenty-one patients undergoing subtotal colectomy with ileorectal anastomosis were included. There were more than 5 large （〉 1 cm） polyps in the remaining rectum （range： 6-20 cm from the anal edge）. All patients, 19 with villous adenomas and 2 with low-grade adenocarcinomas, underwent TEM with submucosal endoscopic excision at least twice between 2005 and 2011. Anorectal manometry and a question- naire about incontinence were carried out at week 1 before operation, and at weeks 2 and 3 and 6 mo after the last operation. Anal resting pressure, maxi- mum squeeze pressure, maximum tolerable volume （MTV） and rectoanal inhibitory reflexes （RAIR） were recorded. The integrity and thickness of the internal anal sphincter （IAS） and external anal sphincter （EAS） were also evaluated by endoanal ultrasonography. We determined the physical and mental health status with SF-36 score to assess the effect of multiple TEM on patient quality of life （QoL）. RESULTS： All patients answered the questionnaire. Apart from negative RAIR in 4 patients, all of the anorectal manometric values in the 21 patients were normal before operation. Mean anal resting pressure decreased from 38±5 mmHg to 19±3 mmHg （38±5 mmHg vs 19±3 mmHg, P = 0.000） and MTV from 165± 19mLto60± 11mL（165± 19mLvs60± 11 mL, P = 0.000） at month 3 after surgery. Anal resting pressure and MTV were 37 ± 5 mmHg （38 ± 5 mmHg vs 37 ± 5 mmHg, P = 0.057） and 159 ± 19 mL （165 ± 19 mL vs 159 ± 19 mL, P = 0.071）, respectively, at month 6 after TEM. Maximal squeeze pressure de- creased from 171 ± 19 mmHg to 62 ± 12 mmHg （171 ± 19 mmHg vs 62 ± 12 mmHg, P = 0.000） at week 2 after operation, and returned to normal values by postoperative month 3 （171 ± 19 vs 166 ± 18, P = 0.051）. RAIR were absent in 4 patients preoperatively and in 12 （χ2 = 4.947, P = 0.026） patients at month 3 after surgery. PAIR was absent only in 5 patients at postoperative month 6 （χ2 = 0.141, P = 0.707）. Endo- sonography demonstrated that IAS disruption occurred in 8 patients, and 6 patients had temporary inconti- nence to flatus that was normalized by postoperative month 3. IAS thickness decreased from 1.9 ± 0.6 mm preoperatively to 1.3 ± 0.4 mm （1.9 ± 0.6 mm vs 1.3 ± 0.4 mm, P = 0.000） at postoperative month 3 and increased to 1.8 ± 0.5 mm （1.9 ± 0.6 mm vs 1.8 ± 0.5 mm, P = 0.239） at postoperative month 6. EAS thickness decreased from 3.7 ± 0.6 mm preoperatively to 3.5 ± 0.3 mm （3.7 ± 0.6 mm vs 3.5 ± 0.3 mm, P = 0.510） at month 3 and then increased to 3.6 ± 0.4 mm （3.7 ± 0.6 mm vs 3.6 ± 0.4 mm, P = 0.123） at month 6 after operation. Most patients had frequent stools per day and relatively high Wexner scores in a short time period. While actual fecal incontinence was exceptional, episodes of soiling were reported by 3 pa- tients. With regard to the QoL, the physical and mental health status scores （SF-36） were 56.1 and 46.2 （50 in the general population）, respectively.CONCLUSION： The anorectal function after repeated TEM is preserved. Multiple TEM procedures are useful for resection of multi-polyps in the remaining rectum.