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Sample records for adenomatous polyposis patients

  1. Familial adenomatous polyposis

    Bülow, Steffen

    1989-01-01

    Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal ana...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation.......Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal...... frequent occurrence of premalignant duodenal adenomas. The prognosis is good after prophylactic colectomy in patients without carcinoma. All first degree relatives of affected family members should be examined regularly with proctosigmoidoscopy from the age of ten, and prophylaxis should be organised using...

  2. Familial adenomatous polyposis

    Bülow, Steffen

    1989-01-01

    Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal ana...... a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposisis a long step forward, and several problems may be solved by increasing international cooperation.......Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal...... frequent occurrence of premalignant duodenal adenomas. The prognosis is good after prophylactic colectomy in patients without carcinoma. All first degree relatives of affected family members should be examined regularly with proctosigmoidoscopy from the age of ten, and prophylaxis should be organised using...

  3. Clinicopathological features of familial adenomatous polyposis in Korean patients

    Jung, Sung Min; Yoon, Yong Sik; Lim, Seok-Byeong; Yu, Chang Sik; Kim, Jin Cheon

    2016-01-01

    AIM: To identify prognostic factors and to correlate APC mutations with clinical features, including extracolic manifestations. METHODS: One hundred thirty-five patients who underwent surgical procedures for familial adenomatous polyposis (FAP) were included. FAP was diagnosed when the number of adenomatous polyps was > 100. Data related to patient, extracoloic manifestations, cancer characteristics, operative procedure, follow up and surveillance were collected. APC mutation testing was performed in the 30 most recent patients. DNA was extracted from peripheral blood and polymerase chain reaction products using 31 primer pairs on APC gene were sequenced. A retrospective study was performed to investigate a causal relationship between prognosis and feature of patient. RESULTS: The mean age of the 51 patients with colorectal cancer (CRC) was older than that of those without CRC (30.5 vs 36.9, P = 0.002). Older individuals were more likely to have colon cancer at the time of FAP diagnosis [odds ratio, 4.75 (95%CI: 1.71-13.89) and 5.91(1.76-22.12) for 40-49 years and age > 50 vs age < 30). The number of confirmed deaths was 13 and the median age at death was 40 years (range, 27 to 85 years). Ten of the deaths (76.9%) were from CRC. Another cause of two cases of death were desmoid tumors (15.4%). Development of cancer on remnant rectal or ileal mucosa after surgery was not observed. The APC mutation testing revealed 23 pathogenic mutations and one likely pathogenic mutation, among which were four novel mutations. The correlation between mutational status and clinical manifestations was investigated. Mutations that could prodict poor prognosis were at codon 1309 which located on mutation cluster region, codon 1465 and codon 1507. CONCLUSION: Identification of APC mutations should aid in the diagnosis and counseling of family members in terms of early diagnosis and management of FAP. PMID:27158207

  4. Familial adenomatous polyposis

    Rozen Paul

    2009-10-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE, desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system. A less aggressive variant of FAP, attenuated FAP (AFAP, is characterized by fewer colorectal adenomatous polyps (usually 10 to 100, later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC gene. Most patients (~70% have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP, which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a

  5. The Pancreas in Familial Adenomatous Polyposis

    Alaa Elkharwily

    2008-01-01

    Full Text Available Familial adenomatous polyposis is an archetypal disease illustrating the genetic basis of human cancer. The adenomatouspolyposis coli gene functions as a tumor suppressor with hundreds of known mutations that result in a defective adenomatous polyposis coli protein. In addition to the certain fate of colon cancer without colectomy, patients with familialadenomatous polyposis are also at increased risk for other types of neoplasms, including those which affect the pancreas. This review focuses on periampullary and ampullary tumors, benign and malignant pancreatic neoplasms that are associated with familial adenomatous polyposis and Gardner syndrome and pancreatitis in these patients. An individualized surveillance regimen is suggested which for certain patients could include endoscopic ultrasound.

  6. The Pancreas in Familial Adenomatous Polyposis

    Alaa Elkharwily; Klaus Gottlieb

    2008-01-01

    Familial adenomatous polyposis is an archetypal disease illustrating the genetic basis of human cancer. The adenomatouspolyposis coli gene functions as a tumor suppressor with hundreds of known mutations that result in a defective adenomatous polyposis coli protein. In addition to the certain fate of colon cancer without colectomy, patients with familialadenomatous polyposis are also at increased risk for other types of neoplasms, including those which affect the pancreas. This review focuses...

  7. Desmoid tumours in familial adenomatous polyposis.

    Gurbuz, A K; Giardiello, F.M.; Petersen, G M; Krush, A J; Offerhaus, G. J.; Booker, S V; Kerr, M.C.; Hamilton, S R

    1994-01-01

    Desmoids are rare, benign fibromatous lesions, which can arise in patients with familial adenomatous polyposis (FAP), a disorder caused by germline adenomatous polyposis coli (APC) gene mutation. This study investigated the risk of desmoids in FAP, the relation between specific APC gene mutations and desmoid formation, and the clinical characteristics of FAP patients with desmoids. Eighty three of 825 FAP patients (10%) from 49 of 161 kindreds (30%) had desmoids. The absolute risk of desmoids...

  8. Controversies in the surgery of patients with familial adenomatous polyposis and Lynch syndrome.

    Church, James M

    2016-07-01

    Dominantly inherited syndromes of colorectal cancer predisposition are characterized by multifocal neoplasia with an early age of onset. The risk of colorectal cancer is high in affected patients and care of the patients is based on the aims of cancer prevention and cancer cure. At the same time, quality of life should be disturbed as little as possible. Because patients are generally young, the stakes are high. Injudicious decision-making can have unfortunate effects on patients and families. In this article the controversial aspects of surgery in familial adenomatous polyposis and Lynch syndrome are discussed. Specifically the controversies in familial adenomatous polyposis include the timing and the type of surgery while for Lynch syndrome discussion revolves about prophylactic surgery, primary, secondary and tertiary. PMID:26869170

  9. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen

    2003-01-01

    Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal with a...

  10. Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

    Familial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations are point mutations or small insertions / deletions which lead to truncated protein products. Splicing mutations or gross genomic rearrangements are less common inactivating events of the APC gene. In the current study genomic DNA or RNA from ten unrelated FAP suspected patients was examined for germline mutations in the APC gene. Family history and phenotype were used in order to select the patients. Methods used for testing were dHPLC (denaturing High Performance Liquid Chromatography), sequencing, MLPA (Multiplex Ligation – dependent Probe Amplification), Karyotyping, FISH (Fluorescence In Situ Hybridization) and RT-PCR (Reverse Transcription – Polymerase Chain Reaction). A 250 Kbp deletion in the APC gene starting from intron 5 and extending beyond exon 15 was identified in one patient. A substitution of the +5 conserved nucleotide at the splice donor site of intron 9 in the APC gene was shown to produce frameshift and inefficient exon skipping in a second patient. Four frameshift mutations (1577insT, 1973delAG, 3180delAAAA, 3212delA) and a nonsense mutation (C1690T) were identified in the rest of the patients. Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations

  11. Deep vein thrombosis in a patient of adenomatous polyposis coli treated successfully with aspirin: A case report

    Agrawal, Neha; Santra, Tuhin; Kar, Arnab; Guha, Pradipta; Bar, Mita; Adhikary, Apu; Datta, Sumana

    2016-01-01

    Background: Deep vein thrombosis is an important cause of morbidity and mortality. However, its association with adenomatous polyposis coli is extremely rare. Here we present an interesting case of deep vein thrombosis associated with adenomatous polyposis coli. Case Presentation: A 15 year old female who was having fever and diarrhea for 5 months developed bilateral asymmetric painful swelling of lower limbs for 1 month. Doppler ultrasound of lower limbs revealed presence of thrombosis from inferior vena cava up to popliteal vein. Colonoscopy and biopsy were suggestive of adenomatous polyposis coli. However, she could not tolerate anticoagulant therapy and was put on aspirin therapy for 6 months to which she responded well with the resolution of thrombus. Conclusion: Role of aspirin therapy may be considered whenever a patient of venous thrombosis cannot tolerate anticoagulant therapy. PMID:27386068

  12. FAMILIAL ADENOMATOUS POLYPOSIS

    XU Ning; DING Yan-qing; XU Li

    1999-01-01

    @@ Clinical History A 41-year-old female was admitted into Nan Fang Hospital for severe abdominal pain with bloody-mucoid stool for a month. The symptoms started a year ago without obvious causes and she did not have any systemic treatment.The patient felt fatigue and loss of weight for the last three months and increased frequency of bloody-mucoid discharge from 2-4 times/day to 10 times/day for the last month. Two weeks ago the patient had a proctoscope with biopsy in Pan Yu people's Hospital. The pathological diagnosis was rectal villous adenoma with focal malignant changes. Rectal examination in this hospital found a rectal mass, 4 cm from the anus, longitudinal growing and occupying a quarter of the circumference. Further colonofiberscope diagnosis was familial polyposis of colon.Family history showed that her father died of lung cancer,her mother died of colonic cancer and her brother and sister were healthy. A total colo-rectectomy with ileostomy was performed.

  13. Two cases of 5q deletions in patients with familial adenomatous polyposis: possible link with Caroli's disease.

    Hodgson, S V; Coonar, A S; P. J. Hanson; Cottrell, S; Scriven, P N; Jones, T; Hawley, P R; Wilkinson, M L

    1993-01-01

    Two cases are reported of patients with deletions of chromosome 5q. Both have familial adenomatous polyposis (FAP) and mild mental retardation. In both, macroscopic polyposis was confined to the proximal colon in adult life (in their thirties) although microscopic adenomatosis was shown in the more distal colon with occasional single polyps. Both subjects had dermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE) was seen in case 2. Case 1 has gastroduodenal polyp...

  14. Diagnosis of familial adenomatous polyposis

    Bülow, Steffen

    1991-01-01

    Familial adenomatous polyposis (FAP) includes early development of up to thousands of colorectal adenomas and of colorectal adenocarcinoma in all untreated cases. Moreover, a variety of extracolonic manifestations are seen. Proctosigmoidoscopy is used for screening; when adenomas are found, the d...... preclinical diagnosis in the future. A centralized registration of FAP has resulted in an improved prognosis, and the establishment of international groups will contribute to increased research of this disease....

  15. Chemoprevention of familial adenomatous polyposis.

    Lynch, Patrick M

    2016-07-01

    Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of "chemoprevention" trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of "clinical benefit", not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints. PMID:27083160

  16. Culture of primary epithelial adenoma cells from familial adenomatous polyposis patients

    Fostira, F.; Apessos, A.; Oikonomou, E.; Kouklis, P.; Baratsis, S.; Manifikos, G.; Anděra, Ladislav; Yannoukakos, D.; Pintzas, A.; Nasioulas, G.

    2008-01-01

    Roč. 28, 2A (2008), s. 843-846. ISSN 0250-7005 Institutional research plan: CEZ:AV0Z50520514 Keywords : colorectal neoplasia * adenomatous polyposis coli * epithelial cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.390, year: 2008

  17. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice

    Liu, Zhen; Qiu, Fangfang; Li, Jing; Zhu, Zhenzhen; Yang, Wenzhao; Zhou, Xiangtian; An, Jianhong; Huang, Furong; Wang, Qiongsi; Reinach, Peter S.; Li, Wei; Chen, Wensheng; Liu, Zuguo

    2015-01-01

    Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible ass...

  18. Causes of death in familial adenomatous polyposis

    Galle, T S; Juel, K; Bülow, S

    1999-01-01

    The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to du...... duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer....

  19. Attenuated familial adenomatous polyposis presenting as ampullary adenocarcinoma

    Trimbath, J.D.; Griffin, C; Romans, K; Giardiello, F M

    2003-01-01

    The risk of periampullary cancer in patients with classic familial adenomatous polyposis (FAP) is significantly increased compared with the general population. However, the incidence of this extracolonic manifestation in attenuated FAP (AFAP) is unknown. We report the case of a 38 year old woman with no known family history of polyposis or colorectal cancer, who presented with ampullary adenocarcinoma. Diagnosis of AFAP was made only after evaluation of the patient’s extended family history a...

  20. Polipose gastroduodenal em doentes com polipose adenomatosa familiar Pós-Retocolectomia Gastroduodenal polyposis in patients with familiar adenomatous polyposis after rectocolectomy

    Raquel Franco Leal

    2007-06-01

    Full Text Available RACIONAL: As manifestações extracólicas, como os pólipos gastroduodenais e o tumor do duodeno, são fatores que influenciam a morbimortalidade dos doentes com polipose adenomatosa familiar no seguimento pós-retocolectomia total. OBJETIVO: Investigar a freqüência destas alterações em doentes com polipose adenomatosa familiar e verificar a eficácia do rastreamento endoscópico. MÉTODO:No período de 1984 a 2005, 62 doentes com polipose adenomatosa familiar pós-retocolectomia foram estudados retrospectivamente pelo Grupo de Coloproctologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, SP. O tempo de seguimento médio pós-operatório foi de 81,9 meses, sendo que em 53 (85,5% foi possível analisar a ocorrência de pólipos gastroduodenais. RESULTADOS: Dos 53 doentes em seguimento, 27 (50,9% apresentavam pólipos gastroduodenais. Em 8 (15,4% os pólipos adenomatosos eram gástricos, 14 (27% pólipos duodenais e 5 (9,6% pólipos gástricos e duodenais. Dois doentes (3,8% desenvolveram adenoma duodenal com displasia de alto grau. E outro (1,9%, adenocarcinoma em papila duodenal. CONCLUSÃO: O rastreamento endoscópico, desta forma, é de grande importância e o objetivo é detectar, o mais precocemente possível, os casos de adenocarcinoma duodenal e pólipos gastroduodenais com displasia de alto grau.BACKGROUND: The extra colonic manifestations, like upper gastrointestinal tract polyps and duodenal cancer are disorders that affect long-term morbidity and mortality of patients with familial adenomatous polyposis, after rectocolectomy. AIM: To describe the frequency of those disorders in patients with familial adenomatous polyposis and to review efficacy of upper gastrointestinal endoscopic surveillance. METHODS: Between 1984 and 2005, 62 patients with familial adenomatous polyposis after rectocolectomy, were studied retrospectively, by Coloproctology Group, Medical Sciences Faculty, State University of Campinas

  1. Ability of FDG-PET to detect all cancers in patients with familial adenomatous polyposis, and impact on clinical management

    Familial adenomatous polyposis (FAP) is characterised by colonic and duodenal adenomatous polyps that carry a risk of malignant transformation. Malignant degeneration of duodenal adenomas is difficult to detect. We speculated that 2-(18F)-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) might be able to detect early duodenal cancer in FAP. Accordingly, we investigated the role of FDG-PET in the management of FAP patients. FDG-PET was performed in 24 FAP patients. Eight had advanced duodenal adenomas (Spigelman IV), including two patients with duodenal cancer. Scans were defined as positive on the basis of focal FDG accumulation. Pathological FDG accumulation was absent in 19 of 24 patients. All six patients with Spigelman IV duodenal adenomas (without cancer) were negative; two of these underwent a duodenectomy and pathological examination did not reveal duodenal cancer. In five patients, FDG-PET revealed significant uptake, in the duodenum (2), lower abdomen (1), lung (1) and multiple sites in the abdomen (1). These hot spots correlated with duodenal cancer (2), abdominal metastasis (1) and sclerosing haemangioma of the lung (1). We failed to make a histopathological diagnosis in the single patient with multiple intra-abdominal sites of FDG uptake. None of the patients from the FDG-PET-negative group developed cancer during follow-up (mean 2.8 years). (orig.)

  2. Rare combination of familial adenomatous polyposis and gallbladder polyps

    MORI, YASUHISA; Sato, Norihiro; Matayoshi, Nobutaka; Tamura, Toshihisa; Minagawa, Noritaka; Shibao, Kazunori; Higure, Aiichiro; Nakamoto, Mitsuhiro; Taguchi, Masashi; Yamaguchi, Koji

    2014-01-01

    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. ...

  3. Familial adenomatous polyposis: from bedside to benchside.

    O'Sullivan, M J

    2012-02-03

    Familial adenomatous polyposis (FAP) is a dominantly inherited cancer-predisposition syndrome with an incidence of between 1:17,000 and 1:5,000. The condition has been causally linked to mutation of the adenomatous polyposis coli (APC) gene located at 5q21. Virtually all mutations in the APC gene are truncating mutations, resulting in loss of function of the APC protein. Spontaneous germline mutation of this gene occurs frequently and accounts for the high incidence of FAP. The gene is somatically mutated at an early point in the colorectal adenoma-carcinoma progression. Somatic mutations of the APC gene are also frequently observed in a variety of other human carcinomas. Isolation of the APC gene has led to the recognition of genotype-phenotype correlations and, together with protein studies, has helped to elucidate the structure and function of the APC protein. This report aims to take the reader from a clinical appreciation to a molecular understanding of FAP.

  4. Surgical treatment in familial adenomatous polyposis

    Tudyka, Vera N.; Clark, Susan K.

    2012-01-01

    Familial adenomatous polyposis (FAP) is a dominantly inherited condition caused by germline mutation of the APC gene resulting in formation of numerous large bowel adenomas in late childhood or adolescence. Unless these are removed, colorectal cancer inevitably develops. Prophylactic surgical treatment is required to prevent this. In surgical decision making, considerations should include genotype-phenotype correlation, perioperative morbidity and risk of impaired sexual and reproductive func...

  5. Age and manifestation related symptoms in familial adenomatous polyposis

    Hohenberger Werner; Reingruber Bertram; Brueckl Wolfgang M; Croner Roland S; Guenther Klaus

    2005-01-01

    Abstract Background To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. Methods We undertook a retrospective study of 143 FAP patients treated at the Department of...

  6. Colectomy and ileorectal anastomosis is still an option for selected patients with familial adenomatous polyposis

    Bülow, Steffen; Bulow, C.; Vasen, H.; Jarvinen, H.; Bjork, J.; Christensen, Ib Jarle

    2008-01-01

    PURPOSE: The risk of rectal cancer after colectomy and ileorectal anastomosis may be reduced in the last decades, as patients with severe polyposis now have an ileoanal pouch. We have reevaluated the risk of rectal cancer and proctectomy for all causes according to the year of operation. METHODS......: On the basis of the year of operation in 776 patients with ileorectal anastomosis and 471 pouch patients in Denmark, Finland, Holland, and Sweden, the "pouch period" was defined to start in 1990. Ileorectal anastomosis follow-up data was captured by May 31, 2006. The cumulative risk of rectal cancer...... and proctectomy was compared before and after 1990 by Kaplan-Meier analysis. RESULTS: In the prepouch period 56/576 patients (10 percent) developed rectal cancer, vs. 4/200 (2 percent) in the pouch period. Neither the cumulative risk of rectal cancer (p = 0.07) nor the cumulative risk of proctectomy...

  7. Attenuated Familial Adenomatous Polyposis (AFAP) Results from an international collaborative study

    Knudsen, A L; Bülow, S; Tomlinson, I; Möslein, G; Heinimann, K; Christensen, I J

    Abstract Aim. The study aimed to describe genetical and clinical features of Attenuated Familial Adenomatous Polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. Method. A questionnaire study was carried out of polyposis registries with data on patients...

  8. Endoscopic Submucosal Dissection for the Complete Resection of the Rectal Remnant Mucosa in a Patient With Familial Adenomatous Polyposis

    Akiyama, Hitoshi; Suzuki, Koyu; Fujita, Yoshiyuki

    2016-01-01

    A 47-year-old woman underwent prophylactic subtotal colectomy with ileorectal anastomosis (IRA) for familial adenomatous polyposis (FAP) 18 years ago. She underwent 5 transanal endoscopic microsurgeries for rectal remnant polyps, and was referred for the treatment of rectal remnant polyp recurrence. Endoscopic submucosal dissection (ESD) was performed to remove multiple polypoid lesions that circumferentially extended throughout the rectal remnant with lesions spreading onto the anastomotic site. The rectal remnant mucosa was resected in 2 pieces without complication. Specimens showed high-grade adenoma but no malignancy. Follow-up colonoscopy showed no recurrence. PMID:27144195

  9. Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis

    Akin, E.; Demirezer Bolat, A.; Buyukasik, S.; Algin, O.; Selvi, E; Ersoy, O.

    2012-01-01

    Objective. The objective of this study was to assess the utility of magnetic resonance enterography (MRE) compared with capsule endoscopy (CE) for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP). Methods. Patients underwent MRE and CE. The polyps were classified according to size of polyp: 10 mm (large size). The location (jejunum or ileum) and the number of polyps (1–5, 6–20, >20) detected by CE were also assessed. MRE findings were compared with the...

  10. Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis

    Perea del Pozo, E.; Ramirez Plaza, C.; J. Padillo Ruiz; J.M. Martos Martínez

    2015-01-01

    Background: Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours Methods and results: We report the case ...

  11. Results of national registration of familial adenomatous polyposis

    Bülow, Steffen

    2003-01-01

    BACKGROUND AND AIMS: The Danish Polyposis Register was established in 1971 with the aim of improving the poor prognosis of familial adenomatous polyposis (FAP), and in 1975 the register became national. The aim of the present study was to evaluate the prevalence of colorectal cancer and survival ...

  12. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

    Vasen, H.F.; Moslein, G.; Alonso, A.; Aretz, S.; Bernstein, I.; Bertario, L.; Blanco, I.; Bulow, S.; Burn, J.; Capella, G.; Colas, C.; Engel, C.; Frayling, I.; Friedl, W.; Hes, F.J.; Hodgson, S.; Jarvinen, H.; Mecklin, J.P.; Moller, P.; Myrhoi, T.; Nagengast, F.M.; Parc, Y.; Phillips, R.; Clark, S.K.; Leon, M.P. de; Renkonen-Sinisalo, L.; Sampson, J.R.; Stormorken, A.; Tejpar, S.; Thomas, H.J.; Wijnen, J.; Vasen, H F A; Möslein, G; Alonso, A; Aretz, S; Bernstein, Inge Thomsen; Bertario, L; Blanco, I; Bülow, Steffen; Burn, J; Capella, G; Colas, C; Engel, C; Frayling, I; Friedl, W; Hes, F J; Hodgson, S; Järvinen, H; Mecklin, J-P; Møller, P; Myrhøi, T; Nagensgast, F M; Parc, Y; Phillips, R; Clark, S K; Ponz de Leon, M; Renkonen-Sinisalo, L; Sampson, J R; Stormorken, A; Tejpar, S; Thomas, H J W; Wijnen, J

    2008-01-01

    BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC...... typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate...

  13. Desmoid tumour in familial adenomatous polyposis. A review of literature

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    Desmoid tumours (DT) are rare benign tumours that do not metastasise, but tend to invade locally. DT are frequently seen in patients with familial adenomatous polyposis (FAP), and diagnosis and treatment are often difficult. Surgical trauma, genetic predisposition and hormonal factors are...... considered to be correlated with the development and growth of DT. In patients with FAP, 50% of the tumours are localised intra-abdominally, and 85-100% of these are mesenteric. DT frequently present as non- tender, slowly growing masses. The symptoms are abdominal pain, vomiting, diarrhoea or haematochezia....... Mesenteric DT can cause small bowel obstruction or ischaemia, hydronephrosis or form fistulas. Diagnosis is obtained through biopsy and the extension is determined by a CT-scan. Surgical excision is recommended in patients with DT in the abdominal wall. First line treatment of mesenteric DT is a NSAID in...

  14. Stability of colon stem cell methylation after neo-adjuvant therapy in a patient with attenuated familial adenomatous polyposis

    Shibata Darryl

    2005-06-01

    Full Text Available Abstract Background Methylation at certain human CpG rich sequences increases with age. The mechanisms underlying such age-related changes are unclear, but methylation may accumulate slowly in a clock-like manner from birth and record lifetime numbers of stem cell divisions. Alternatively, methylation may fluctuate in response to environmental stimuli. The relative stability of methylation patterns may be inferred through serial observations of the same colon. Case presentation A 22 year-old male with attenuated familial adenomatous polyposis received neo-adjuvant chemotherapy and radiation prior to surgery for rectal adenocarcinoma. Colon crypt methylation patterns before and after neo-adjuvant therapy (62 days apart were essentially identical with respect to percent methylation and diversity. Consistent with previous studies, methylation patterns recorded no evidence for enhanced colon crypt stem cell survival with a germline mutation (codon 215 proximal to the mutation cluster region of APC. Conclusion The inability of neo-adjuvant therapy to significantly alter crypt methylation patterns suggests stem cells are relatively protected from transient environmental changes. Age-related methylation appears to primarily reflect epigenetic errors in stem cells that slowly accumulate in a clock-like manner from birth. Therefore, life-long human stem cell histories are potentially written within and may be read from somatic cell epigenomes.

  15. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice.

    Zhen Liu

    Full Text Available Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP, havean adenomatous polyposis coli (APC mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR and customized optical coherence tomography (OCT. Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D on P84 which was associated with increased vitreous chamber depth (VCD. Furthermore, retinal and scleral changes appear in these mice along with: 1 axial length shortening; 2 increased retinal cell proliferation; 3 and decreased tyrosine hydroxylase (TH expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1 expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development.

  16. Adenomatous Polyposis Coli Mutation Leads to Myopia Development in Mice

    Li, Jing; Zhu, Zhenzhen; Yang, Wenzhao; Zhou, Xiangtian; An, Jianhong; Huang, Furong; Wang, Qiongsi; Reinach, Peter S.; Li, Wei; Chen, Wensheng; Liu, Zuguo

    2015-01-01

    Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT) littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR) and customized optical coherence tomography (OCT). Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D) on P84 which was associated with increased vitreous chamber depth (VCD). Furthermore, retinal and scleral changes appear in these mice along with: 1) axial length shortening; 2) increased retinal cell proliferation; 3) and decreased tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1) expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development. PMID:26495845

  17. [Adenomatous polyposis of the gallbladder and Gardner's syndrome. A rare association].

    Brevet, Marie; Brehant, Olivier; Dumont, Frédéric; Regimbeau, Jean-Marc; Dupas, Jean-Louis; Chatelain, Denis

    2007-04-01

    We report one case of adenomatous polyposis of the gallbladder in a 57 year-old woman with Gardner's syndrome presenting with cholangitis. On gross examination the gallbladder contained two calculi and numerous flat or polypoid adenomas less than 1 cm in size. On microscopic examination, the adenomas showed low and high grade intraepithelial neoplasia. Only 10 cases of gallbladder adenomas have been reported in the literature in patients presenting with familial adenomatous polyposis (FAP). Cholecystectomy is usually performed for cholecystitis or cholangitis. These adenomatous gallbladder lesions are discovered late, often when the patient is older than 40. Pathogenesis of gallbladder adenomas is still unclear. It is difficult to assess the risk of malignancy: only 6 cases of gallbladder adenocarcinomas have been reported in patients with FAP. PMID:17483782

  18. Adenoma development in familial adenomatous polyposis and MUTYH-associated polyposis: somatic landscape and driver genes.

    Rashid, Mamunur; Fischer, Andrej; Wilson, Cathy H; Tiffen, Jessamy; Rust, Alistair G; Stevens, Philip; Idziaszczyk, Shelley; Maynard, Julie; Williams, Geraint T; Mustonen, Ville; Sampson, Julian R; Adams, David J

    2016-01-01

    Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss-of-function mutations in WTX (9%; p < 9.99e-06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. PMID:26414517

  19. Age and manifestation related symptoms in familial adenomatous polyposis

    Hohenberger Werner

    2005-03-01

    Full Text Available Abstract Background To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. Methods We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. Results FAP was diagnosed clinically on the basis of symptoms in 84% (120/143 of these patients. Most presented with intestinal symptoms such as colonic bleeding (68% and diarrhea (42%. All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76, whereas in those over 40 years old the prevalence was 76% (35/46. Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. Conclusion The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

  20. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

    Duffy, M

    2012-02-03

    PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are

  1. Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis

    E. Akin

    2012-01-01

    Full Text Available Objective. The objective of this study was to assess the utility of magnetic resonance enterography (MRE compared with capsule endoscopy (CE for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP. Methods. Patients underwent MRE and CE. The polyps were classified according to size of polyp: 10 mm (large size. The location (jejunum or ileum and the number of polyps (1–5, 6–20, >20 detected by CE were also assessed. MRE findings were compared with the results of CE. Results. Small-bowel polyps, were detected by CE in 4 of the 6 (66% patients. Three patients had small-sized polyps and one patient had medium-sized polyps. CE detected polyps in four patients that, were not shown on MRE. Desmoid tumors were detected on anterior abdominal wall by MRE. Conclusion. In patients with FAP, CE can detect small-sized polyps in the small intestine not seen with MRE whereas MRE yields additional extraintestinal information.

  2. Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

    Buecher, Bruno

    2016-02-01

    Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. PMID:26805944

  3. Characterization of an APC Promoter 1B deletion in a Patient Diagnosed with Familial Adenomatous Polyposis via Whole Genome Shotgun Sequencing [v1; ref status: indexed, http://f1000r.es/5i1

    Ted Kalbfleisch

    2015-06-01

    Full Text Available Recently, deletions have been identified and published as causal for Familial Adenomatous Polyposis in the 1B promoter region of the APC gene.  Those deletions were measured using multiplex ligation-dependent probe amplification.  Here, we present and characterize an ~11kb deletion identified by whole genome shotgun sequencing.  The deletion occurred in a patient diagnosed with Familial Adenomatous Polyposis, and was located on chr5, between bases 112,034,824 and 112,045,845, fully encompassing the 1B promoter region of the APC gene.   Results are presented here that include the sequence evidence supporting the presence of the deletion as well as base level characterization of the deletion site.  These results demonstrate the capacity of whole genome sequencing for the detection of large structural variants in single individuals.

  4. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management

    Leoz ML

    2015-04-01

    Full Text Available Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP. FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC, and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

  5. Subsequent Adenomas of Ileal Pouch and Anorectal Segment after Prophylactic Surgery for Familial Adenomatous Polyposis

    M'Koma, A.E.; Herline, A.J.; Adunyah, S.E.

    2013-01-01

    Familial adenomatous polyposis (FAP) is an autosomally dominant disease characterized by the early development of colorectal adenomas and carcinoma in untreated patients. Patients with FAP may develop rectal cancer at their initial presentation (primary) or after prophylactic surgery (secondary). Controversies exist regarding which surgical procedure represents the best first-line treatment. The options for FAP are ileorectal anastomosis (IRA) or a restorative proctocolectomy (RPC) with eithe...

  6. Sulphomucin expression in ileal pouches: emerging differences between ulcerative colitis and familial adenomatous polyposis pouches.

    Bambury, Niamh

    2012-02-03

    PURPOSE: We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. METHODS: Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. RESULTS: High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 +\\/- 0.5 vs. 0.556 +\\/- 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. CONCLUSIONS: Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation.

  7. Structural basis of the Axin–adenomatous polyposis coli interaction

    Spink, Katharine Eklof; Polakis, Paul; Weis, William I.

    2000-01-01

    Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene β-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3β (GSK3β) and several other proteins. Both Axin and APC are known to be critical for β-catenin regulation, and truncations in APC that eliminate the Axin-b...

  8. Pigmented mesenteric lymphadenopathy in familial adenomatous polyposis - an unusual cause of intraoperative abandonment of ileo-anal pouch.

    Pranesh, N; Haboubi, N Y; O'Dwyer, S T

    2005-01-01

    Familial adenomatous polyposis (FAP) is an autosomal dominant condition with near complete penetrance, characterised by the presence of numerous adenomatous polyps of the colon and rectum. Melanosis coli describes the brownish-black discolouration of the colon resulting from the accumulation of a granular pigment in the phagosomes of macrophages in the colonic lamina propria. The presence of melanosis pigment in pericolonic lymph nodes has been reported in patients with coincidental melanosis...

  9. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, F.J.; Ruano, D.; Nieuwenhuis, M.; Tops, C.M.; Schrumpf, M.; Nielsen, M.; Huijts, P.E.; Wijnen, J.T.; Wagner, A.; Garcia, E.B.; Sijmons, R.H.; Menko, F.H.; Letteboer, T.G.; Hoogerbrugge, N.; Harryvan, J.; Kampman, E.; Morreau, H.; Vasen, H.F.; Wezel, T. van

    2014-01-01

    BACKGROUND: Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC

  10. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, Frederik J.; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M.; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E. A.; Wijnen, Juul T.; Wagner, Anja; Gomez Garcia, Encarna B.; Sijmons, Rolf H.; Menko, Fred H.; Letteboer, Tom G. W.; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F. A.; van Wezel, Tom

    2014-01-01

    Background Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20-30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC

  11. Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis

    E. Perea del Pozo

    2015-01-01

    Conclusions: The diagnosis of CMV of PTC is very strongly related to the FAP syndrome and must be suspected when a thyroid node appears in FAP patients. Likewise, any patient without known FAP who presents this histology in a surgically biopsied or resected thyroid node should undergo total colonoscopy for screening of colonic polyposis and genetic study of the APC gene sequence.

  12. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    develop colorectal cancer, but the lifetime risk of upper gastrointestinal cancer is lower, estimated at approximately 5%. Management of the upper gastrointestinal cancer risk is one of the greatest challenges facing clinicians involved in the care of Polyposis families, and with improved survival......Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop foregut as well as hindgut polyps, and following prophylactic colectomy duodenal cancer constitutes one of the leading causes of death in screened populations. Without prophylactic colectomy, FAP patients predictably...... following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments in...

  13. Variation of a variation: Case report of attenuated familial adenomatous polyposis

    Bhatnagar, P; Tetzlaff, H.; Izatt, L; Devlin, J; Heaton, N. D.

    2006-01-01

    Background. First described in 1988, attenuated familial adenomatous polyposis (AFAP) is a rare autosomal dominant precancerous condition of the gastrointestinal tract. Few reports have described adenocarcinomatous change in the gastroduodenal region thus far. Case outlineWe report a case of AFAP presenting with extensive gastric polyposis and ampullary adenocarcinoma in absence of a positive family history of gastrointestinal cancer and a novel mutation.

  14. Andalusian Registry for Familial Adenomatous Polyposis: Analysis of patients included Registro Andaluz de la Poliposis Adenomatosa Familiar: Análisis de los pacientes incluidos

    M. Garzón Benavides

    2010-11-01

    Full Text Available Objective: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. Material and methods: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. Results: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51 and 46 relatives at risk with a mean age of 21.8 years (6-55. Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC at the time of diagnosis (32.2%. Only two affected relatives showed CRC at diagnosis (4.3%, a statistically significant difference (p Objetivos: Valorar las características fenotípicas y genotípicas de los pacientes incluidos en el Registro Andaluz de la poliposis adenomatosa familiar, la relación genotipo/fenotipo y el impacto del Registro en la frecuencia de cáncer colorrectal de los familiares registrados. Material y métodos: Estudio descriptivo de 77 pacientes con PAF, pertenecientes a 33 familias, incluidos en una base de datos centralizada a la que tienen acceso los responsables de los hospitales participantes, previa firma de cartas de confidencialidad. Todos los estudios genéticos se realizan en el Servicio de Inmunología de nuestro Hospital. Resultados: 77 pacientes registrados (50,6% varones: 31 probandos, edad media: 32 años (13-51 y 46 familiares afectos, edad media 21,8 años (6-55. Estudio genético informado en 68/77 con resultado positivo en 92,6%. Cáncer colorrectal al diagnóstico en diez probandos (32,2% y 2 familiares afectos (4,3%, diferencia estad

  15. [Familial adenomatous polyposis: establishing a registry and genetic and molecular analysis].

    Shomrat, R; Bruchim, R; Galanty, Y; Samuel, Z; Legum, C; Rabau, M; Rozen, P

    1997-01-15

    Familial adenomatous polyposis (FAP), a dominantly inherited disease, is caused by a mutation in the adenomatous polyposis coli gene in chromosome 5q21. The gene has 15 exons, a physical length of 10 Kb and an open reading frame of 8.5 Kb. Exon 15 codes 66% of the mRNA and has a mutation cluster region which accounts for over 50% of mutations. The disease usually leads to the appearance of hundreds of adenomatous polyps in the transverse and descending colon between puberty and age 20 years and to colon cancer before the age of 40. Early detection is essential to prevent the development of metastasizing cancer. Since 1994 we have recruited 23 families for genetic counseling. DNA was obtained from 19 unrelated FAP patients and 219 high risk relatives in 19 unrelated families following confirmation of the diagnosis. In addition to linkage studies, direct mutational analysis was performed using the protein truncation test for most of exon 15 and single strand conformation polymorphism analysis for the other exons. These exons account for most of the mutations identified to date. Of 19 unrelated probands, 14 had detectable mutations. Exon 15 accounted for 6 families, exons 5, 7 and 14 for 1 each, exon 9 for 3, and exon 8 for 2. Combined mutational and linkage analysis identified 18 presymptomatic carriers who received genetic and clinical counseling. Our FAP patients did not differ significantly from those of larger studies in other countries with regard to the distribution of the mutations, gender and genotype-phenotype correlation, or ethnic distribution. PMID:9119305

  16. Dietary Putrescine Reduces the Anticarcinogenic Intestinal Activity of Sulindac in a Murine Model of Familial Adenomatous Polyposis

    Ignatenko, Natalia A.; Besselsen, David G; Basu Roy, Upal K.; Stringer, David E.; Blohm-Mangone, Karen A.; Padilla-Torres, Jose L.; Guillen-R, Jose M.; Gerner, Eugene W.

    2006-01-01

    The nonsteroidal antiinflammatory drug sulindac displays chemopreventive activity in patients with familial adenomatous polyposis (FAP). Sulindac metabolites induce apoptosis in colon tumor cells, in part, by a polyamine-dependent mechanism that can be suppressed with exogenous putrescine. To determine the relevance of this mechanism in animals, we treated ApcMin/+ mice, a model of human FAP, with sulindac alone or in combination with dietary putrescine. Sulindac increased steady-state RNA le...

  17. Colonic Crypt Changes during Adenoma Development in Familial Adenomatous Polyposis : Immunohistochemical Evidence for Expansion of the Crypt Base Cell Population

    Boman, Bruce M; Walters, Rhonda; Fields, Jeremy Z.; Kovatich, Albert J.; Zhang, Tao; Isenberg, Gerald A.; Goldstein, Scott D.; Palazzo, Juan P.

    2004-01-01

    Familial adenomatous polyposis patients, who have a germline APC mutation, develop adenomas in normal-appearing colonic mucosa, and in the process usually acquire a mutation in the other APC allele as well. Nonetheless, the cellular mechanisms that link these initiating genetic changes with the earliest tissue changes (upward shift in the labeling index) in colon tumorigenesis are unclear. Based on the tenet that colorectal cancer originates from crypt stem cells (SCs) and on our kinetic mode...

  18. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    Hes, Frederik J; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E A; Wijnen, Juul T; Wagner, Anja; Gómez García, Encarna B; Sijmons, Rolf H; Menko, Fred H; Letteboer, Tom G W; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F A; van Wezel, Tom

    2013-01-01

    Background Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20–30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas. Methods We analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs). Results We found a statistically significant association with two of the variants tested: rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC. Conclusions These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance. PMID:24253443

  19. Familial Adenomatous Polyposis in Three Generations of a Single Family: A Case Study

    Jure Murgic

    2014-05-01

    Full Text Available Background: Familial adenomatous polyposis (FAP is an autosomal dominantly inherited syndrome characterized by the development of numerous polyps in the colon and rectum. If left untreated, the affected patients inevitably develop colon cancer by the age of 40 years. A resection of the colon (colectomy or of the colon and rectum (proctocolectomy is needed to minimize the risk of cancer. Case Presentation: We report a case of FAP through three generations of a single family, in which the grandmother and granddaughter underwent total colectomy with ileoanal anastomosis and did not develop colon cancer, while the son underwent subtotal colectomy with ileorectal anastomosis and developed recurrent rectal cancer. Data regarding timely surgery, surveillance, and chemoprevention are discussed. Conclusion: The FAP phenotype determines the type of treatment. In severe polyposis, proctocolectomy with ileoanal anastomosis seems to be the optimal method for minimizing the risk of cancer development. This case report advocates complete rectal removal, especially in cases of poor patient compliance with colonoscopic surveillance.

  20. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome

    Christina Lui; Myth T. S. Mok; Henderson, Beric R.

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT) growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained...

  1. A novel function of adenomatous polyposis coli (APC) in regulating DNA repair

    Jaiswal, Aruna S.; Narayan, Satya

    2008-01-01

    Prevailing literature suggests diversified cellular functions for the adenomatous polyposis coli (APC) gene. Among them a recently discovered unique role of APC is in DNA repair. The APC gene can modulate the base excision repair (BER) pathway through an interaction with DNA polymerase β (Pol-β) and flap endonuclease 1 (Fen-1). Taken together with the transcriptional activation of APC gene by alkylating agents and modulation of BER activity, APC may play an important role in carcinogenesis an...

  2. A novel SYBR-based duplex qPCR for the detection of gene dosage: detection of an APC large deletion in a familial adenomatous polyposis patient with an unusual phenotype

    Torrezan Giovana

    2012-07-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is a hereditary colorectal cancer syndrome caused by a loss of function of the APC gene. Large deletions in APC are a common cause of FAP; despite the existence of a variety of gene dosage detection methodologies, most are labor intensive and time and resource consuming. Methods We describe a new duplex qPCR method for gene dosage analysis based on the coamplification of a target and a reference gene in a SYBR Green reaction, followed by a comparison of the ratio between the target and the reference peaks of the melting curve for the test (patient and control samples. The reliability of the described duplex qPCR was validated for several genes (APC, HPRT1, ATM, PTEN and BRCA1. Results Using this novel gene dosage method, we have identified an APC gene deletion in a FAP patient undergoing genetic testing. Comparative genomic hybridization based on microarrays (aCGH was used to confirm and map the extent of the deletion, revealing a 5.2 MB rearrangement (5q21.3-q22.3 encompassing the entire APC and 19 additional genes. Conclusion The novel assay accurately detected losses and gains of one copy of the target sequences, representing a reliable and flexible alternative to other gene dosage techniques. In addition, we described a FAP patient harboring a gross deletion at 5q21.3-q22.3 with an unusual phenotype of the absence of mental impairment and dysmorphic features.

  3. Desmoid Tumor Associated With Familial Adenomatous Polyposis: Evaluation With 64-Detector CT Enterography

    Desmoid tumors (DTs) are benign tumors which are not seen very often, and most of the radiologists and clinicians do not know the characteristics of them very well. Correct and early diagnosis of DTs is important for decreasing mortality and morbidity. Computed tomography enterography (CTE) is a new modality for small bowel imaging which combines the improved spatial and temporal resolution of multidetector computed tomography (CT) with large volumes of ingested enteric contrast material to permit evaluation of the small bowel wall and lumen and also the entire abdomen. We report a familial adenomatous polyposis (FAP) patient with localized mesentery and abdominal wall DTs. We showed the exact location of the DTs and their relation with the small bowel by CTE. In conclusion, CTE is a useful technique for DT localization, the degree of extension and invasion to local structures, presence of partial and complete small bowel obstruction, and the relationship of the tumors with vasculature and whether ischemia has occurred as a result or not

  4. Desmoid Tumor Associated With Familial Adenomatous Polyposis: Evaluation With 64-Detector CT Enterography

    Oktay Algin

    2012-03-01

    Full Text Available Desmoid tumors (DTs are benign tumors which are not seen very often, and most of the radiologists and clinicians do not know the characteristics of them very well. Correct and early diagnosis of DTs is important for decreasing mortality and morbidity. Computed tomography enterography (CTE is a new modality for small bowel imaging which combines the improved spatial and temporal resolution of multidetector computed tomography (CT with large volumes of ingested enteric contrast material to permit evaluation of the small bowel wall and lumen and also the entire abdomen. We report a familial adenomatous polyposis (FAP patient with localized mesentery and abdominal wall DTs. We showed the exact location of the DTs and their relation with the small bowel by CTE. In conclusion, CTE is a useful technique for DT localization, the degree of extension and invasion to local structures, presence of partial and complete small bowel obstruction, and the relationship of the tumors with vasculature and whether ischemia ha s occurred as a result or not.

  5. Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate.

    Septer, Seth; Lawson, Caitlin E; Anant, Shrikant; Attard, Thomas

    2016-07-01

    Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also require surveillance. In infants and toddlers, there is an increased risk of hepatoblastoma, while in teenagers and adults duodenal carcinomas, desmoid tumors, thyroid cancer and medulloblastoma are more common in FAP than in the general population. Current chemopreventive strategies include several medications and natural products, although to this point there is no consensus on the most efficacious and safe agent. Genetic counseling is an important part of the diagnostic process for FAP. Appropriate use and interpretation of genetic testing is best accomplished with genetic counselor involvement as many families also have concerns regarding future insurability or discrimination when faced with genetic testing. PMID:27056662

  6. Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

    Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (APC) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of APC promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and APC promoter methylation. For evaluating the status of APC promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated APC promoter was compared with that of unmethylated patients. Assessment of APC promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of APC. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of APC. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of

  7. Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.

    Adam, Ronja; Spier, Isabel; Zhao, Bixiao; Kloth, Michael; Marquez, Jonathan; Hinrichsen, Inga; Kirfel, Jutta; Tafazzoli, Aylar; Horpaopan, Sukanya; Uhlhaas, Siegfried; Stienen, Dietlinde; Friedrichs, Nicolaus; Altmüller, Janine; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Kayser, Katrin; Thiele, Holger; Holinski-Feder, Elke; Marra, Giancarlo; Kristiansen, Glen; Nöthen, Markus M; Büttner, Reinhard; Möslein, Gabriela; Betz, Regina C; Brieger, Angela; Lifton, Richard P; Aretz, Stefan

    2016-08-01

    In ∼30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we performed exome sequencing of leukocyte DNA from 102 unrelated individuals with unexplained adenomatous polyposis. We identified two unrelated individuals with differing compound-heterozygous loss-of-function (LoF) germline mutations in the mismatch-repair gene MSH3. The impact of the MSH3 mutations (c.1148delA, c.2319-1G>A, c.2760delC, and c.3001-2A>C) was indicated at the RNA and protein levels. Analysis of the diseased individuals' tumor tissue demonstrated high microsatellite instability of di- and tetranucleotides (EMAST), and immunohistochemical staining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effect and causal relevance of the mutations. The pedigrees, genotypes, and frequency of MSH3 mutations in the general population are consistent with an autosomal-recessive mode of inheritance. Both index persons have an affected sibling carrying the same mutations. The tumor spectrum in these four persons comprised colorectal and duodenal adenomas, colorectal cancer, gastric cancer, and an early-onset astrocytoma. Additionally, we detected one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mismatch-repair deficiency. Potentially causative variants in 14 more candidate genes identified in 26 other individuals require further workup. In the present study, we identified biallelic germline MSH3 mutations in individuals with a suspected hereditary tumor syndrome. Our data suggest that MSH3 mutations represent an additional recessive subtype of colorectal adenomatous polyposis. PMID:27476653

  8. Genetic basis of hereditary colorectal cancers: Hereditary nonpolyposis colorectal cancer and Familial adenomatous polyposis

    Renkonen, Elise

    2006-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are characterized by a high risk and early onset of colorectal cancer (CRC). HNPCC is due to a germline mutation in one of the following MMR genes: MLH1, MSH2, MSH6 and PMS2. A majority of FAP and attenuated FAP (AFAP) cases are due to germline mutations of APC, causing the development of multiple colorectal polyps. To date, over 450 MMR gene mutations and over 800 APC mutations have been identified. Mo...

  9. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats; Johannsson, Oskar; Rambech, Eva; Mangell, Peter

    2008-01-01

    ABSTRACT: Background Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined ...

  10. Duodenal adenoma surveillance in patients with familialadenomatous polyposis

    2015-01-01

    Familial adenomatous polyposis (FAP) is a hereditarydisorder caused by Adenomatous Polyposis Genemutations that lead to the development of colorectalpolyps with great malignant risk throughout life. Moreover,numerous extracolonic manifestations incorporatedifferent clinical features to produce varied individualphenotypes. Among them, the occurrence of duodenaladenomatous polyps is considered an almost inevitableevent, and their incidence rates increase as a patient'sage advances. Although the majority of patients exhibitdifferent grades of duodenal adenomatosis as theyage, only a small proportion (1%-5%) of patients willultimately develop duodenal carcinoma. Within thiscontext, the aim of the present study was to reviewthe data regarding the epidemiology, classification,genetic features, endoscopic features, carcinogenesis,surveillance and management of duodenal polyps inpatients with FAP.

  11. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Johannsson Oskar

    2008-11-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Methods Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. Results 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.

  12. Comparison of proctocolectomy and ileal pouch-anal anastomosis to colectomy and ileorectal anastomosis in familial adenomatous polyposis.

    Koskenvuo, L; Mustonen, H; Renkonen-Sinisalo, L; Järvinen, H J; Lepistö, A

    2015-06-01

    Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61%) colectomies with IRA and 88 (39%) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21%) patients after IRA and in 26 (30%) patients after IPAA. There were 15 (11%) severe complications for IRA and 5 (6%) for IPAA. Twenty-one (15%) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4%) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis. PMID:25504366

  13. Colonic and duodenal flat adenomas in children with classical familial adenomatous polyposis.

    Cohen, Marta; Thomson, Mike; Taylor, Chris; Donatone, Jorge; Quijano, Graciela; Drut, Ricardo

    2006-04-01

    Flat adenomas of the colon and duodenum have been described as associating with familial adenomatous polyposis (FAP), its attenuated variant, and the so-called hereditary nonpolyposis colorectal cancer. There seem to be no report on the occurrence of flat adenomas in pediatric patients with family history of FAP. We are reporting 4 children from 2 cancer-prone families in whom colonic and duodenal moderately dysplastic flat adenomas were found. Gastrointestinal endoscopy and biopsies were performed in 3 female siblings (7, 9, and 11 years old) and 1 male (9 years old) when referred for screening owing to familial history of bowel cancer (family 1) or evidence of bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE), which is known to be associated with FAP (family 2). Endoscopic visualization of the mucosa was improved by use of 0.2% indigo carmine solution spray. Biopsies were routinely processed for H&E and immunohistochemistry staining. Present patients were asymptomatic, with the exception of 2 weeks rectal bleeding in 1 of them. The colonic videoendoscopy showed in 2/3 siblings hundreds of flat or slightly raised plaques less than 1 cm in diameter as well as some classic polyps throughout the colon. The other sibling showed 40 flat-topped lesions with minimal elevation and central umbilication in the cecum. Upper endoscopy demonstrated a few flat lesions in the nonperiampullary area of the duodenum in 2/4 patients. The colonic videoendoscopy performed on the 9-year-old boy revealed multiple small sessile polyps. Microscopic study demonstrated tubular adenomas with a few neoplastic crypts, slight disarray of the overall architecture, and moderate (low-grade) dysplasia of the epithelium. These features were more obvious at the center and superficial areas of the adenomas. The 4 children had multiple flat adenomas of the colon and duodenum (2/4) matching with those described in adult patients. Flat adenomas in the context of FAP probably

  14. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

  15. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Price David J; Mason John O; Chen Yijing; Ivaniutsin Uladzislau; Pratt Thomas

    2009-01-01

    Abstract Background Adenomatous polyposis coli (Apc) is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferat...

  16. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Ivaniutsin, Uladzislau; CHEN, Yijing; John O. MASON; Price, David; Pratt, Thomas

    2009-01-01

    Background: Adenomatous polyposis coli (Apc) is a large multifunctional protein known to be important for Wnt/beta-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex.Results: We used Emx1(Cre) to inactivate Apc specifically in proliferating...

  17. Different Roles for the Axin Interactions with the SAMP versus the Second Twenty Amino Acid Repeat of Adenomatous Polyposis Coli

    Schneikert, Jean; Ruppert, Jan Gustav; Behrens, Jürgen; Wenzel, Eva Maria

    2014-01-01

    Wnt signalling is prevented by the proteosomal degradation of β-catenin, which occurs in a destruction complex containing adenomatous polyposis coli (APC), APC-like (APCL), Axin and Axin2. Truncating mutations of the APC gene result in the constitutive stabilisation of β-catenin and the initiation of colon cancer, although tumour cells tolerate the expression of wild-type APCL. Using the colocalisation of overexpressed Axin, APC and APCL constructs as a readout of interaction, we found that A...

  18. The Adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes Axin's interaction with Dishevelled

    Mendoza-Topaz, Carolina; Mieszczanek, Juliusz; Bienz, Mariann

    2011-01-01

    Most cases of colorectal cancer are linked to mutational inactivation of the Adenomatous polyposis coli (APC) tumour suppressor. APC downregulates Wnt signalling by enabling Axin to promote the degradation of the Wnt signalling effector β-catenin (Armadillo in flies). This depends on Axin's DIX domain whose polymerization allows it to form dynamic protein assemblies (‘degradasomes’). Axin is inactivated upon Wnt signalling, by heteropolymerization with the DIX domain of Dishevelled, which rec...

  19. Adenomatous polyposis coli mutants dominantly activate Hsf1-dependent cell stress pathways through inhibition of microtubule dynamics

    Davies, Alexander E.; Kortright, Kaitlyn; Kaplan, Kenneth B.

    2015-01-01

    Cancer cells up-regulate cell stress pathways, including the protein chaperone Hsp90. Increases in Hsp90 are believed “buffer” mutant protein activities necessary for cancer phenotypes. Activation of the cell stress pathway also alters the transcriptional landscape of cells in ways that are critical for cancer progression. However, it is unclear when and how the cell stress pathway is de-regulated during cancer progression. Here we report that mutations in adenomatous polyposis coli (APC) fou...

  20. Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

    Van der Auwera, I; Laere, S.J.; Van den Bosch, S M; Van den Eynden, G. G.; Trinh, B X; van Dam, P A; Colpaert, C G; van Engeland, M; Van Marck, E A; Vermeulen, P B; Dirix, L Y

    2008-01-01

    Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype. The status of APC gene promoter hypermethylation was investigated in DNA from normal b...

  1. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  2. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome.

    Lui, Christina; Mok, Myth T S; Henderson, Beric R

    2016-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT) growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained at the centrosome during interphase suggesting a rapid rate of exchange. This was confirmed in living cells by fluorescence recovery after photobleaching (FRAP), which identified two pools of green fluorescent protein (GFP)-APC: a major rapidly exchanging pool (~86%) and minor retained pool (~14%). The dynamic exchange rate of APC was unaffected by C-terminal truncations implicating a targeting role for the N-terminus. Indeed, we mapped centrosome localization to N-terminal armadillo repeat (ARM) domain amino acids 334-625. Interestingly, the rate of APC movement to the centrosome was stimulated by intact MTs, and APC dynamics slowed when MTs were disrupted by nocodazole treatment or knockdown of γ-tubulin. Thus, the rate of APC recycling at the centrosome is enhanced by MT growth, suggesting a positive feedback to stimulate its role in MT growth. PMID:27144584

  3. Characterization of Adenomatous Polyposis Coli Protein Dynamics and Localization at the Centrosome

    Christina Lui

    2016-04-01

    Full Text Available The adenomatous polyposis coli (APC tumor suppressor is a multifunctional regulator of Wnt signaling and acts as a mobile scaffold at different cellular sites. APC was recently found to stimulate microtubule (MT growth at the interphase centrosome; however, little is known about its dynamics and localization at this site. To address this, we analysed APC dynamics in fixed and live cells by fluorescence microscopy. In detergent-extracted cells, we discovered that APC was only weakly retained at the centrosome during interphase suggesting a rapid rate of exchange. This was confirmed in living cells by fluorescence recovery after photobleaching (FRAP, which identified two pools of green fluorescent protein (GFP-APC: a major rapidly exchanging pool (~86% and minor retained pool (~14%. The dynamic exchange rate of APC was unaffected by C-terminal truncations implicating a targeting role for the N-terminus. Indeed, we mapped centrosome localization to N-terminal armadillo repeat (ARM domain amino acids 334–625. Interestingly, the rate of APC movement to the centrosome was stimulated by intact MTs, and APC dynamics slowed when MTs were disrupted by nocodazole treatment or knockdown of γ-tubulin. Thus, the rate of APC recycling at the centrosome is enhanced by MT growth, suggesting a positive feedback to stimulate its role in MT growth.

  4. Structural basis for the recognition of Asef by adenomatous polyposis coli

    Zhenyi Zhang; Ping Xu; Jian Zhang; Geng Wu; Leyi Chen; Lei Gao; Kui Lin; Liang Zhu; Yang Lu; Xiaoshan Shi; Yuan Gao; Jing Zhou

    2012-01-01

    Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Aset),which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains.The APC-activated Asef stimulates the small GTPase Cdc42,which leads to decreased cell-cell adherence and enhanced cell migration.In colorectal cancers,truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis.Here,we report crystal structures of the human APC/Asef complex.We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef,conformation of which changes dramatically upon binding to APC.Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays.Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between AsefDH domain and APC,which possibly leads to a conformational change in Asef that stimulates its GEF activity.Our structures thus elucidate the molecular mechanism of Asef recognition by APC,as well as provide a potential target for pharmaceutical intervention against cancers.

  5. The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis.

    Duncan, Rony E; Gillam, Lynn; Savulescu, Julian; Williamson, Robert; Rogers, John G; Delatycki, Martin B

    2010-03-01

    Predictive genetic tests for familial adenomatous polyposis (FAP) are routinely offered to young people during early adolescence. While this is not controversial, due to the medical benefit conferred by the test, it is nonetheless challenging as a consequence of the stage of life of the young people, and the simultaneous involvement of multiple family members. Despite these challenges, it is possible to ensure that the test is offered in such a way that it actively acknowledges and facilitates young people's developing autonomy and psychosocial well-being. In this paper we present findings from ten in-depth interviews with young people who have undergone predictive genetic testing for FAP (four male, six female; five gene-positive, five gene-negative; aged 10-17 years at the time of their predictive test; aged 12-25 years at the time of their research interview). We present five themes that emerged from the interviews which highlight key ethical challenges associated with such testing. These are: (1) the significance of the test; (2) young people's lack of involvement in the decision to be tested; (3) young people's limited understanding; (4) provision of the blood test at the first visit; and (5) group testing of family members. We draw on these themes to make eight recommendations for future practice. Together, these recommendations highlight the importance of providing developmentally appropriate care to young people undergoing predictive genetic testing for FAP. PMID:19760114

  6. Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

    Calabrese, Carlo; Rizzello, Fernando; Gionchetti, Paolo; Calafiore, Andrea; Pagano, Nico; De Fazio, Luigia; Valerii, Maria Chiara; Cavazza, Elena; Strillacci, Antonio; Comelli, Maria Cristina; Poggioli, Gilberto; Campieri, Massimo; Spisni, Enzo

    2016-06-01

    Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented blend of phytoestrogens and indigestible insoluble fibers (ADI) help the management of FAP patients with ileal pouch-anal anastomosis (IPAA). In a prospective open label study, we enrolled 15 FAP patients with IPAA and duodenal polyps who underwent upper gastrointestinal endoscopy at baseline and after 3 months of treatment. The primary endpoint was the change in gene expression in polyp mucosa, whereas the secondary endpoint was the reduction in polyp number and size. After 3 months of ADI treatment, all patients showed a reduction in the number and size of duodenal polyps (P = 0.021). Analysis of the expression of CRC promoting/inhibiting genes in duodenal polyps biopsies demonstrated that different CRC-promoting genes (PCNA, MUC1 and COX-2) were significantly downregulated, whereas CRC-inhibiting genes (ER-β and MUC2) were significantly upregulated after ADI treatment. In conclusion, ADI proved to be safe and effective, and its long-term effects on FAP patients need further investigation. Judging from the results we observed on COX-2 and miR-101 expression, the short-term effects of ADI treatment could be comparable with those obtained using COX-2 inhibitors, with the advantage of being much more tolerable in chronic therapies and void of adverse events. PMID:27207660

  7. Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology

    Martin Bortlík; Ivana Vítková; Martina Pape(z)ová; Milada Kohoutová; Ale(s) Novotn(y); Stanislav Adamec; Petra Chalupná; Milan Luká(s)

    2006-01-01

    AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas.METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential,location of adenomas, macroscopic appearance and age of the patients.RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 ± 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 ± 15.5mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P =0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P =0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas.CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation.Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.

  8. A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis

    Burn, John; Bishop, D Timothy; Chapman, Pamela D;

    2011-01-01

    significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus......Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a...... 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design...

  9. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A.; Greaves, Bradford D.; Vinson, David; Roberts, David M.; McCartney, Brooke M.

    2015-01-01

    The colon cancer tumor suppressor Adenomatous polyposis coli (APC) negatively regulates Wnt signaling destruction complex by binding to β-catenin and facilitating its phosphorylation and degradation. The two SAMP repeats and their phosphorylation state in Drosophila APC2 play distinct roles in negatively regulating Wnt signaling.

  10. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

    Li, Jun; Woods, Susan L; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R M; Spurdle, Amanda B; Simpson, Peter T; da Silva, Leonard; Lakhani, Sunil R; Clouston, Andrew D; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F; Wen, Xiaogang; Martin, Hilary C; Neklason, Deborah W; Davis, Sean R; Walker, Robert L; Calzone, Kathleen A; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N; Hulick, Peter J; Weissman, Scott M; Newlin, Anna; Rubinstein, Wendy S; Sampson, Jone E; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K; Huntsman, David G; Foulkes, William D; Carneiro, Fatima; Lindor, Noralane M; Edwards, Stacey L; French, Juliet D; Waddell, Nicola; Meltzer, Paul S; Worthley, Daniel L; Schrader, Kasmintan A; Chenevix-Trench, Georgia

    2016-05-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present. PMID:27087319

  11. Apical Membrane Localization of the Adenomatous Polyposis Coli Tumor Suppressor Protein and Subcellular Distribution of the β-Catenin Destruction Complex in Polarized Epithelial Cells

    Reinacher-Schick, Anke; Gumbiner, Barry M.

    2001-01-01

    The adenomatous polyposis coli (APC) protein is implicated in the majority of hereditary and sporadic colon cancers. APC is known to function as a tumor suppressor through downregulation of β-catenin as part of a high molecular weight complex known as the β-catenin destruction complex. The molecular composition of the intact complex and its site of action in the cell are still not well understood. Reports on the subcellular localization of APC in various cell systems have differed significant...

  12. A proposed staging system and stage-specific interventions for familial adenomatous polyposis

    Lynch, Patrick M; Morris, Jeffrey S; Wen, Sijin;

    2016-01-01

    scores were within ±1 stage of the mode. Sixty percent agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. CONCLUSIONS: The proposed FAP colon polyposis staging system and stage-specific intervention is based on a high degree of agreement on the part of experts in the...... polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical-benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention...... classification scheme for lower GI tract polyposis. METHODS: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case using the proposed system and chose a stage-specific intervention for...

  13. Clinical aspects of patients with nasal polyposis

    Crespo, Cassio Caldini

    2009-09-01

    Full Text Available Introduction: The nasal Polyposis is a non-neoplastic chronic inflammatory process of the nasal mucosa. It causes a large impact to the patients' life quality. Objective: To analyze the characteristics of patients with polyposis in the Brazilian population. Method: 50 records of patients followed up in a tertiary hospital and submitted to surgical treatment of nasal polyposis were reviewed. The following variables were analyzed: age, sex, smoking, presence of asthma, presence of AAS intolerance and also the clinical manifestations: anterior and posterior rhinorrhea, nasal obstruction, hyposmia, sneezing and pruritus. The tomographic evaluation system applied was that of Lund-McKay. For statistical analysis we applied the chi-square test with p<0.05. Results: Out of 50 patients evaluated, 28 were male and 22 were female. The mean age range was of 40.8 years. The main clinical manifestation was nasal obstruction in 100% of the patients. In the tomographic evaluation, according to the Lund-McKay system, the average scoring was of 10.9. Discussion: No statistically significant difference was obtained in the patients' general symptoms compared to the patients with asthma or AAS intolerance. The difference in the Lund-McKay score was statistically significant in the populations studied. The symptoms were similar to the frequency of symptoms of other works. Conclusion: We concluded that the main complaint of the patients with nasal polyposis is nasal obstruction, the most affected age is of about 40 years old, without preference of sex. The severity of tomographic findings is higher in patients with asthma and AAS intolerance.

  14. Adenomatous polyposis coli (APC) regulates multiple signaling pathways by enhancing glycogen synthase kinase-3 (GSK-3) activity.

    Valvezan, Alexander J; Zhang, Fang; Diehl, J Alan; Klein, Peter S

    2012-02-01

    Glycogen synthase kinase-3 (GSK-3) is essential for many signaling pathways and cellular processes. As Adenomatous Polyposis Coli (APC) functions in many of the same processes, we investigated a role for APC in the regulation of GSK-3-dependent signaling. We find that APC directly enhances GSK-3 activity. Furthermore, knockdown of APC mimics inhibition of GSK-3 by reducing phosphorylation of glycogen synthase and by activating mTOR, revealing novel roles for APC in the regulation of these enzymes. Wnt signaling inhibits GSK-3 through an unknown mechanism, and this results in both stabilization of β-catenin and activation of mTOR. We therefore hypothesized that Wnts may regulate GSK-3 by disrupting the interaction between APC and the Axin-GSK-3 complex. We find that Wnts rapidly induce APC dissociation from Axin, correlating with β-catenin stabilization. Furthermore, Axin interaction with the Wnt co-receptor LRP6 causes APC dissociation from Axin. We propose that APC regulates multiple signaling pathways by enhancing GSK-3 activity, and that Wnts induce APC dissociation from Axin to reduce GSK-3 activity and activate downstream signaling. APC regulation of GSK-3 also provides a novel mechanism for Wnt regulation of multiple downstream effectors, including β-catenin and mTOR. PMID:22184111

  15. The Adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes Axin's interaction with Dishevelled.

    Mendoza-Topaz, Carolina; Mieszczanek, Juliusz; Bienz, Mariann

    2011-11-01

    Most cases of colorectal cancer are linked to mutational inactivation of the Adenomatous polyposis coli (APC) tumour suppressor. APC downregulates Wnt signalling by enabling Axin to promote the degradation of the Wnt signalling effector β-catenin (Armadillo in flies). This depends on Axin's DIX domain whose polymerization allows it to form dynamic protein assemblies ('degradasomes'). Axin is inactivated upon Wnt signalling, by heteropolymerization with the DIX domain of Dishevelled, which recruits it into membrane-associated 'signalosomes'. How APC promotes Axin's function is unclear, especially as it has been reported that APC's function can be bypassed by overexpression of Axin. Examining apc null mutant Drosophila tissues, we discovered that APC is required for Axin degradasome assembly, itself essential for Armadillo downregulation. Degradasome assembly is also attenuated in APC mutant cancer cells. Notably, Axin becomes prone to Dishevelled-dependent plasma membrane recruitment in the absence of APC, indicating a crucial role of APC in opposing the interaction of Axin with Dishevelled. Indeed, co-expression experiments reveal that APC displaces Dishevelled from Axin assemblies, promoting degradasome over signalosome formation in the absence of Wnts. APC thus empowers Axin to function in two ways-by enabling its DIX-dependent self-assembly, and by opposing its DIX-dependent copolymerization with Dishevelled and consequent inactivation. PMID:22645652

  16. different Roles for the axin interactions with the SAMP versus the second twenty amino acid repeat of adenomatous polyposis coli.

    Schneikert, Jean; Ruppert, Jan Gustav; Behrens, Jürgen; Wenzel, Eva Maria

    2014-01-01

    Wnt signalling is prevented by the proteosomal degradation of β-catenin, which occurs in a destruction complex containing adenomatous polyposis coli (APC), APC-like (APCL), Axin and Axin2. Truncating mutations of the APC gene result in the constitutive stabilisation of β-catenin and the initiation of colon cancer, although tumour cells tolerate the expression of wild-type APCL. Using the colocalisation of overexpressed Axin, APC and APCL constructs as a readout of interaction, we found that Axin interacted with the second twenty amino acid repeat (20R2) of APC and APCL. This interaction involved a domain adjacent to the C-terminal DIX domain of Axin. We identified serine residues within the 20R2 of APCL that were involved in Axin colocalisation, the phosphorylation of truncated APCL and the down-regulation of β-catenin. Our results indicated that Axin, but not Axin2, displaced APC, but not APCL, from the cytoskeleton and stimulated its incorporation into bright cytoplasmic dots that others have recognised as β-catenin destruction complexes. The SAMP repeats in APC interact with the N-terminal RGS domain of Axin. Our data showed that a short domain containing the first SAMP repeat in truncated APC was required to stimulate Axin oligomerisation. This was independent of Axin colocalisation with 20R2. Our data also suggested that the RGS domain exerted an internal inhibitory constraint on Axin oligomerisation. Considering our data and those from others, we discuss a working model whereby β-catenin phosphorylation involves Axin and the 20R2 of APC or APCL and further processing of phospho-β-catenin occurs upon the oligomerisation of Axin that is induced by binding the SAMP repeats in APC. PMID:24722208

  17. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  18. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  19. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats;

    2008-01-01

    spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031ins......AA) developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP...... cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer....

  20. Attenuated Familial Adenomatous Polyposis (AFAP) Results from an international collaborative study

    Knudsen, A L; Bülow, S; Tomlinson, I;

    2010-01-01

    with presumed AFAP, defined as having /= 25. Results. One hundred and ninety six patients were included. The median number of adenomas was 25 (0-100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty...

  1. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle;

    2012-01-01

    Background and aim: Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

  2. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle;

    2012-01-01

    Background and aim:  Duodenal adenomatosis in FAP results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study is to present results of long-term duodenal surveillance and to evaluate the risk of...... (interquartile range 9-17). The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI 84-93), and of Spigelman stage IV 35% (95% CI 25-45). The Spigelman stage improved in 32 (12%), remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty patients (7%) had duodenal cancer at a median age of...

  3. Prevention of Aspirin against Recurrence of Polyposis after Operation on Patients with Familial Polyposis Coli

    Zhou Jia-zhen; Liu Tao; Jin Jia-gui; Hu Xian-dian

    2006-01-01

    Objective To investigate how well a combined therapy prevents and treats familial polyposis coli and to observe whether aspirin prevents duodenal polyp development after operation.Methods Aspirin was started one month after the operation on 6 patients with familial polyposis coli. It was given 60 mg once a day for one month, and then was discontinued for one month, then used again for one month, and then discontinued for one month; in this way, aspirin was used every two months for the patient's life. The follow-up was performed for 17 years. Results The combined therapy, which consisted of a surgical operation of cutting the superior mesenteric artery & vein and making anastomosis of the ileum pouch and the anal canal within the muscular sheath of the rectum and an internal medical therapy of nonsteroidal antiinflammatory drugs, had a good therapeutic effect on familial polyposis coli and no duodenal polyp occurred in the 6 patients. Conclusion Our combined therapy can effectively treat familial polyposis coli, and aspirin can prevent duodenal polyp development after the operation.

  4. Sense of smell in patients with bilateral nasal polyposis

    Savović Slobodan N.

    2004-01-01

    Full Text Available Introduction Sense of smell is susceptible to various changes, both in physiological and in numerous pathological conditions. Of quantitative disorders of smell, hyposmia and anosmia are quite common, whereas of qualitative disorders parosmia is most frequent. The aim of this paper was to examine impact of bilateral nasal polyposis on olfactory function. Material and methods The research was carried out at the Nose, Ear and Throat Clinic in Novi Sad. It included 80 examinees, 40 (20 male, 20 female with bilateral nasal polyposis, while 40 examinees belonged to the control group (20 male, 20 female without symptoms of nasal polyposes. Fortunato-Niccolini olfactometer was used for this examination. Results and discussion In patients with bilateral nasal polyposis the average perception threshold values for examined odors were 15.50 ccm of odorous air, while in the control group they were 10,20 ccm of odorous air. The average identification threshold values for examined odors in patients with bilateral nasal polyposis were 18.80 ccm of odorous air, while in the control group they were 13.55 ccm of scented air. T-test showed that values of both tresholds were statistically significantly higher (p< 0,01 in patients with bilateral nasal polyposis in relation to the control group. Conclusion Olfactory deficit in patients with bilateral nasal polyposis is explained by difficult or impossible passage of odors into the olfactory region.

  5. Attenuated Familial Adenomatous Polyposis

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... AFAP is suspected when a person has a history of more than 20, but fewer than 100, ...

  6. Familial Adenomatous Polyposis

    ... the inside of a person’s colon form a mass on the inside of the intestinal tract. The ... that does not metastasize; papillary thyroid cancer ; pancreatic , adrenal , and bile duct tumors; and a type of ...

  7. HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction.

    Tran, Hoanh; Bustos, Daisy; Yeh, Ronald; Rubinfeld, Bonnee; Lam, Cynthia; Shriver, Stephanie; Zilberleyb, Inna; Lee, Michelle W; Phu, Lilian; Sarkar, Anjali A; Zohn, Irene E; Wertz, Ingrid E; Kirkpatrick, Donald S; Polakis, Paul

    2013-02-01

    The adenomatous polyposis coli (APC) protein functions as a negative regulator of the Wnt signaling pathway. In this capacity, APC forms a "destruction complex" with Axin, CK1α, and GSK3β to foster phosphorylation of the Wnt effector β-catenin earmarking it for Lys-48-linked polyubiquitylation and proteasomal degradation. APC is conjugated with Lys-63-linked ubiquitin chains when it is bound to Axin, but it is unclear whether this modification promotes the APC-Axin interaction or confers upon APC an alternative function in the destruction complex. Here we identify HectD1 as a candidate E3 ubiquitin ligase that modifies APC with Lys-63 polyubiquitin. Knockdown of HectD1 diminished APC ubiquitylation, disrupted the APC-Axin interaction, and augmented Wnt3a-induced β-catenin stabilization and signaling. These results indicate that HectD1 promotes the APC-Axin interaction to negatively regulate Wnt signaling. PMID:23277359

  8. Colorectal neoplasia in juvenile polyposis or juvenile polyps.

    Giardiello, F.M.; Hamilton, S R; Kern, S. E.; Offerhaus, G. J.; Green, P A; Celano, P.; Krush, A J; Booker, S V

    1991-01-01

    Juvenile (retention) polyps are usually solitary lesions in the colorectum but may be multiple in juvenile polyposis. The association between juvenile polyps and colorectal neoplasia is controversial. We present three patients with juvenile polyposis who had colorectal adenomas or adenomatous epithelium in juvenile polyps at ages 3, 4, and 7 years. In a retrospective study of 57 additional patients with one or more juvenile polyps, 10 patients (18%) had colorectal neoplasia including three wi...

  9. Clinical and ethical implications of genetic counselling in familial adenomatous polyposis Implicaciones clínicas y éticas del consejo genético en la poliposis adenomatosa familiar

    A. Fernández-Suárez

    2005-09-01

    Full Text Available The association of specific genetic disturbances with the development of hereditary cancer helps us to understand the risk of suffering from it, the possibility of an earlier diagnosis, and the treatment and prevention of this disease. Familial adenomatous polyposis (FAP is a pre-neoplastic syndrome characterized by the presence of hundreds of adenomatous polyps in the colon, which develop into a carcinoma. FAP can be diagnosed using sequencing techniques to detect mutations in the germinal line of the APC (adenomatous polyposis coli gene. The genetic diagnostic approach in families with FAP, previously followed up in the Gastrointestinal Clinic, has both advantages and disadvantages, and places us nearer the disease and patient. Disclosing the results of this genetic test entails relevant problems in clinical practice, which affect the health field and raise legal and ethical issues, along with the familial, occupational, and social implications that knowing the genetic status can have on the patient. Genetic analysis is rare in normal clinical practice, which involves errors in the interpretation of the results obtained, and during the process of genetic counselling. Specialized multidisciplinary units are necessary for the management of patients with FAP undergoing analysis and appropriate genetic counselling, thus providing an individualized service. The creation of FAP registers and protocols for this healthcare process should optimize the management of these patients and their families.La asociación de determinadas alteraciones genéticas con la aparición de cáncer hereditario, nos permite conocer el riesgo de padecerlo, posibilitando el diagnóstico precoz, el tratamiento y la prevención de la enfermedad. La poliposis adenomatosa familiar (PAF es un síndrome preneoplásico que se caracteriza por la presencia de cientos de pólipos adenomatosos en colon, que evolucionarán hacia carcinoma. La PAF puede ser diagnosticada mediante t

  10. Evaluación económica de la prueba genética de la poliposis adenomatosa familiar An economic assessment of genetic testing for familial adenomatous polyposis

    A. Olry de Labry Lima

    2008-08-01

    Full Text Available Objetivo: analizar el coste-utilidad de la prueba genética a familiares de primer grado de pacientes con cáncer de colon para determinar mutaciones del gen APC (Adenomatous Polyposis Coli. Metodología: los análisis se realizaron desde el punto de vista del sistema sanitario. Se utilizó un modelo de Markov. Realización de la prueba genética para el gen APC, causante de la poliposis adenomatosa familiar (PAF, que produce cáncer de colon frente a la no realización de la misma. La medida de efectividad utilizada fueron los años de vida ajustados por calidad (AVAC y la unidad de coste los euros de 2005. Los costes de las intervenciones fueron extraídos de los precios públicos de los servicios sanitarios prestados por centros dependientes del Sistema Sanitario Público Andaluz y los valores de la efectividad y de utilidad de la literatura. Resultados: la realización de la prueba genética se muestra como una estrategia dominante a la no realización de la misma, ya que esta última tiene un coste incremental de 7.676,34 €, además de una menor efectividad. Los análisis de sensibilidad mostraron que la realización de la prueba genética se mantiene como la estrategia dominante dentro de un amplio rango de coste de la prueba y de probabilidad de desarrollar adenocarcinomas. Conclusiones: los análisis mostraron que, para este grupo de pacientes, la realización de la prueba genética para la detección de la mutación del gen APC es en promedio menos costosa y además produce una mejora en AVAC comparado con la no realización de la misma.Objective: to analyze the cost-effectiveness of genetic testing for first-degree relatives of patients with colon cancer to identify mutations in the APC gene (Adenomatous Polyposis Coli. Methodology: analyses were performed from the perspective of the health system. We used a Markov model. We compared genetic testing for the APC gene, the cause of familial adenomatous polyposis (FAP, which results in

  11. Lymphoid enhancer factor-1 blocks adenomatous polyposis coli-mediated nuclear export and degradation of beta-catenin. Regulation by histone deacetylase 1.

    Henderson, Beric R; Galea, Melanie; Schuechner, Stefan; Leung, Louie

    2002-07-01

    The oncogenic protein beta-catenin is overexpressed in many cancers, frequently accumulating in nuclei where it forms active complexes with lymphoid enhancer factor-1 (LEF-1)/T-cell transcription factors, inducing genes such as c-myc and cyclin D1. In normal cells, nuclear beta-catenin levels are controlled by the adenomatous polyposis coli (APC) protein through nuclear export and cytoplasmic degradation. Transient expression of LEF-1 is known to increase nuclear beta-catenin levels by an unknown mechanism. Here, we show that APC and LEF-1 compete for nuclear beta-catenin with opposing consequences. APC can export nuclear beta-catenin to the cytoplasm for degradation. In contrast, LEF-1 anchors beta-catenin in the nucleus by blocking APC-mediated nuclear export. LEF-1 also prevented the APC/CRM1-independent nuclear export of beta-catenin as revealed by in vitro assays. Importantly, LEF-1-bound beta-catenin was protected from degradation by APC and axin in SW480 colon cancer cells. The ability of LEF-1 to trap beta-catenin in the nucleus was down-regulated by histone deacetylase 1, and this correlated with a decrease in LEF1 transcription activity. Our findings identify LEF-1 as key regulator of beta-catenin nuclear localization and stability and suggest that overexpression of LEF-1 in colon cancer and melanoma cells may contribute to the accumulation of oncogenic beta-catenin in the nucleus. PMID:11986304

  12. Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the β-catenin destruction complex.

    Tran, Hoanh; Polakis, Paul

    2012-08-17

    The adenomatous polyposis coli (APC) tumor suppressor forms a complex with Axin and GSK3β to promote the phosphorylation and degradation of β-catenin, a key co-activator of Wnt-induced transcription. Here, we establish that APC is modified predominantly with K63-linked ubiquitin chains when it is bound to Axin in unstimulated HEK293 cells. Wnt3a stimulation induced a time-dependent loss of K63-polyubiquitin adducts from APC, an effect synchronous with the dissociation of Axin from APC and the stabilization of cytosolic β-catenin. RNAi-mediated depletion of Axin or β-catenin, which negated the association between APC and Axin, resulted in the absence of K63-adducts on APC. Overexpression of wild-type and phosphodegron-mutant β-catenin, combined with analysis of thirteen human cancer cell lines that harbor oncogenic mutations in APC, Axin, or β-catenin, support the hypothesis that a fully assembled APC-Axin-GSK3β-phospho-β-catenin complex is necessary for the K63-polyubiquitylation of APC. Intriguingly, the degree of this modification on APC appears to correlate inversely with the levels of β-catenin in cells. Together, our results indicate that K63-linked polyubiquitin adducts on APC regulate the assembly and/or efficiency of the β-catenin destruction complex. PMID:22761442

  13. The two SAMP repeats and their phosphorylation state in Drosophila Adenomatous polyposis coli-2 play mechanistically distinct roles in negatively regulating Wnt signaling.

    Kunttas-Tatli, Ezgi; Von Kleeck, Ryan A; Greaves, Bradford D; Vinson, David; Roberts, David M; McCartney, Brooke M

    2015-12-01

    The tumor suppressor Adenomatous polyposis coli (APC) plays a key role in regulating the canonical Wnt signaling pathway as an essential component of the β-catenin destruction complex. C-terminal truncations of APC are strongly implicated in both sporadic and familial forms of colorectal cancer. However, many questions remain as to how these mutations interfere with APC's tumor suppressor activity. One set of motifs frequently lost in these cancer-associated truncations is the SAMP repeats that mediate interactions between APC and Axin. APC proteins in both vertebrates and Drosophila contain multiple SAMP repeats that lack high sequence conservation outside of the Axin-binding motif. In this study, we tested the functional redundancy between different SAMPs and how these domains are regulated, using Drosophila APC2 and its two SAMP repeats as our model. Consistent with sequence conservation-based predictions, we show that SAMP2 has stronger binding activity to Axin in vitro, but SAMP1 also plays an essential role in the Wnt destruction complex in vivo. In addition, we demonstrate that the phosphorylation of SAMP repeats is a potential mechanism to regulate their activity. Overall our findings support a model in which each SAMP repeat plays a mechanistically distinct role but they cooperate for maximal destruction complex function. PMID:26446838

  14. Adenomatous polyposis coli-mediated control of β-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors

    Löwik Clemens WGM

    2009-04-01

    Full Text Available Abstract Background During skeletogenesis, protein levels of β-catenin in the canonical Wnt signaling pathway determine lineage commitment of skeletal precursor cells to osteoblasts and chondrocytes. Adenomatous polyposis coli (Apc is a key controller of β-catenin turnover by down-regulating intracellular levels of β-catenin. Results To investigate whether Apc is involved in lineage commitment of skeletal precursor cells, we generated conditional knockout mice lacking functional Apc in Col2a1-expressing cells. In contrast to other models in which an oncogenic variant of β-catenin was used, our approach resulted in the accumulation of wild type β-catenin protein due to functional loss of Apc. Conditional homozygous Apc mutant mice died perinatally showing greatly impaired skeletogenesis. All endochondral bones were misshaped and lacked structural integrity. Lack of functional Apc resulted in a pleiotropic skeletal cell phenotype. The majority of the precursor cells lacking Apc failed to differentiate into chondrocytes or osteoblasts. However, skeletal precursor cells in the proximal ribs were able to escape the noxious effect of functional loss of Apc resulting in formation of highly active osteoblasts. Inactivation of Apc in chondrocytes was associated with dedifferentiation of these cells. Conclusion Our data indicate that a tight Apc-mediated control of β-catenin levels is essential for differentiation of skeletal precursors as well as for the maintenance of a chondrocytic phenotype in a spatio-temporal regulated manner.

  15. The postsynaptic adenomatous polyposis coli (APC) multiprotein complex is required for localizing neuroligin and neurexin to neuronal nicotinic synapses in vivo.

    Rosenberg, Madelaine M; Yang, Fang; Mohn, Jesse L; Storer, Elizabeth K; Jacob, Michele H

    2010-08-18

    Synaptic efficacy requires that presynaptic and postsynaptic specializations align precisely and mature coordinately. The underlying mechanisms are poorly understood, however. We propose that adenomatous polyposis coli protein (APC) is a key coordinator of presynaptic and postsynaptic maturation. APC organizes a multiprotein complex that directs nicotinic acetylcholine receptor (nAChR) localization at postsynaptic sites in avian ciliary ganglion neurons in vivo. We hypothesize that the APC complex also provides retrograde signals that direct presynaptic active zones to develop in register with postsynaptic nAChR clusters. In our model, the APC complex provides retrograde signals via postsynaptic neuroligin that interacts extracellularly with presynaptic neurexin. S-SCAM (synaptic cell adhesion molecule) and PSD-93 (postsynaptic density-93) are scaffold proteins that bind to neuroligin. We identify S-SCAM as a novel component of neuronal nicotinic synapses. We show that S-SCAM, PSD-93, neuroligin and neurexin are enriched at alpha3*-nAChR synapses. PSD-93 and S-SCAM bind to APC and its binding partner beta-catenin, respectively. Blockade of selected APC and beta-catenin interactions, in vivo, leads to decreased postsynaptic accumulation of S-SCAM, but not PSD-93. Importantly, neuroligin synaptic clusters are also decreased. On the presynaptic side, there are decreases in neurexin and active zone proteins. Further, presynaptic terminals are less mature structurally and functionally. We define a novel neural role for APC by showing that the postsynaptic APC multiprotein complex is required for anchoring neuroligin and neurexin at neuronal synapses in vivo. APC human gene mutations correlate with autism spectrum disorders, providing strong support for the importance of the association, demonstrated here, between APC, neuroligin and neurexin. PMID:20720115

  16. Downregulation of adenomatous polyposis coli by microRNA-663 promotes odontogenic differentiation through activation of Wnt/beta-catenin signaling

    Highlights: • miR-663 is significantly up-regulated during MDPC-23 odontoblastic cell differentiation. • miR-663 accelerates mineralization in MDPC-23 odontoblastic cells without cell proliferation. • miR-663 promotes odontoblastic cell differentiation by targeting APC and activating Wnt/β-catenin signaling in MDPC-23 cells. - Abstract: MicroRNAs (miRNAs) regulate cell differentiation by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontogenic differentiation is largely unknown. In this present study, we observed that the expression of miR-663 increased significantly during differentiation of MDPC-23 cells to odontoblasts. Furthermore, up-regulation of miR-663 expression promoted odontogenic differentiation and accelerated mineralization without proliferation in MDPC-23 cells. In addition, target gene prediction for miR-663 revealed that the mRNA of the adenomatous polyposis coli (APC) gene, which is associated with the Wnt/β-catenin signaling pathway, has a miR-663 binding site in its 3′-untranslated region (3′UTR). Furthermore, APC expressional was suppressed significantly by miR-663, and this down-regulation of APC expression triggered activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Taken together, these findings suggest that miR-663 promotes differentiation of MDPC-23 cells to odontoblasts by targeting APC-mediated activation of Wnt/β-catenin signaling. Therefore, miR-663 can be considered a critical regulator of odontoblast differentiation and can be utilized for developing miRNA-based therapeutic agents

  17. Downregulation of adenomatous polyposis coli by microRNA-663 promotes odontogenic differentiation through activation of Wnt/beta-catenin signaling

    Kim, Jae-Sung; Park, Min-Gyeong; Lee, Seul Ah; Park, Sun-Young; Kim, Heung-Joong; Yu, Sun-Kyoung; Kim, Chun Sung; Kim, Su-Gwan; Oh, Ji-Su; You, Jae-Seek; Kim, Jin-Soo; Seo, Yo-Seob [Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759 (Korea, Republic of); Chun, Hong Sung [Department of Biomedical Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Joo-Cheol [Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 110-749 (Korea, Republic of); Kim, Do Kyung, E-mail: kdk@chosun.ac.kr [Oral Biology Research Institute, School of Dentistry, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2014-04-18

    Highlights: • miR-663 is significantly up-regulated during MDPC-23 odontoblastic cell differentiation. • miR-663 accelerates mineralization in MDPC-23 odontoblastic cells without cell proliferation. • miR-663 promotes odontoblastic cell differentiation by targeting APC and activating Wnt/β-catenin signaling in MDPC-23 cells. - Abstract: MicroRNAs (miRNAs) regulate cell differentiation by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontogenic differentiation is largely unknown. In this present study, we observed that the expression of miR-663 increased significantly during differentiation of MDPC-23 cells to odontoblasts. Furthermore, up-regulation of miR-663 expression promoted odontogenic differentiation and accelerated mineralization without proliferation in MDPC-23 cells. In addition, target gene prediction for miR-663 revealed that the mRNA of the adenomatous polyposis coli (APC) gene, which is associated with the Wnt/β-catenin signaling pathway, has a miR-663 binding site in its 3′-untranslated region (3′UTR). Furthermore, APC expressional was suppressed significantly by miR-663, and this down-regulation of APC expression triggered activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Taken together, these findings suggest that miR-663 promotes differentiation of MDPC-23 cells to odontoblasts by targeting APC-mediated activation of Wnt/β-catenin signaling. Therefore, miR-663 can be considered a critical regulator of odontoblast differentiation and can be utilized for developing miRNA-based therapeutic agents.

  18. Evaluación económica de la prueba genética de la poliposis adenomatosa familiar An economic assessment of genetic testing for familial adenomatous polyposis

    A. Olry de Labry Lima; L. Sordo del Castillo; L. García Mochón; Epstein, D; C. Bermúdez Tamayo; R. Villegas Portero

    2008-01-01

    Objetivo: analizar el coste-utilidad de la prueba genética a familiares de primer grado de pacientes con cáncer de colon para determinar mutaciones del gen APC (Adenomatous Polyposis Coli). Metodología: los análisis se realizaron desde el punto de vista del sistema sanitario. Se utilizó un modelo de Markov. Realización de la prueba genética para el gen APC, causante de la poliposis adenomatosa familiar (PAF), que produce cáncer de colon frente a la no realización de la misma. La medida de efe...

  19. Manifestações extracolônicas da polipose adenomatosa familiar: incidência e impacto na evolução da doença Extracolonic manifestations of familial adenomatous polyposis: incidence and impact on the disease outcome

    Fábio Guilherme Campos

    2003-06-01

    Full Text Available RACIONAL: A polipose adenomatosa familiar é doença hereditária de caráter autossômico dominante, que freqüentemente se associa a numerosas manifestações extracolônicas. OBJETIVOS: Relatar a incidência de manifestações extracolônicas em nosso meio e analisar seu impacto na evolução da doença. PACIENTES E MÉTODOS: Revisão dos prontuários de pacientes com polipose adenomatosa familiar tratados no período de 1977 a 2001, relatando as manifestações extracolônicas associadas e suas complicações. RESULTADOS: Dos 59 pacientes com polipose adenomatosa familiar, 23 (38,9% apresentaram alguma manifestação extracolônica por ocasião do diagnóstico ou no seguimento. Foram registradas 37 diferentes manifestações (1,6 por paciente. As mais comuns foram osteomas e alterações na pigmentação da retina, diagnosticadas em 25% e 20% dos pacientes pesquisados, respectivamente. Outras manifestações extracolônicas achadas foram adenomas do trato digestivo superior, cistos epidermóides, tumores desmóides (sete cada, câncer gástrico (três e câncer de tireóide (dois. Complicações importantes diretamente relacionadas aos tumores desmóides foram reportadas em seis pacientes, sendo obstrução intestinal em quatro e hidronefrose em dois. Registraram-se óbitos em dois pacientes (28,5%. CONCLUSÕES: A incidência de manifestações extracolônicas é alta (40%, podendo afetar a evolução da doença e a qualidade de vida dos pacientes. Por esses motivos, torna-se de fundamental importância a pesquisa, a prevenção e o tratamento adequado dessas manifestações na polipose adenomatosa familiar.BACKGROUND: Familial adenomatous polyposis is a hereditary disease with autossomic and dominant features, frequently associated to many extracolonic manifestations. AIM: To report extracolonic manifestations incidence and to analyze its impact on the disease's outcome. PATIENTS AND METHODS: Revision of patient charts treated from 1977 to

  20. Prevalence of colorectal adenomatous polyps in patients with chronic obstructive pulmonary disease

    Chun EM

    2015-05-01

    Full Text Available Eun Mi Chun, Seo Woo Kim, So Yeon Lim Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea Background: Colorectal adenomatous polyps are precancerous lesions of colorectal cancer. The aim of this study was to assess the prevalence of colorectal adenomatous polyps in chronic obstructive pulmonary disease (COPD patients and determine whether COPD is associated with colorectal malignant potential.Methods: Subjects who had undergone post-bronchodilator spirometry and colonoscopy and were 40 years or older were selected from the hospital database. COPD was defined as a spirometry in which the ratio of forced expiratory volume in 1 second (FEV1 and forced vital capacity (FVC is <0.7 in post-bronchodilator spirometry. The non-COPD group was matched for both age and sex, and were defined as having an FEV1, FVC, and FEV1/FVC ≥0.7 in spirometry. Finally, 333 patients were retrospectively reviewed; of this group, 82 patients had COPD.Results: Among the subjects, 201 patients (60% were nonsmokers, while 78 (23% were current smokers. The prevalence of colorectal adenomatous polyps was 39% (98/251 in the non-COPD group and 66% (54/82 in the COPD group. Among 54 patients with adenomatous polyps in the COPD group, 47 had tubular adenoma and seven had villous adenoma. Multiple logistic regression analyses revealed that only COPD patients whom matched to the criteria of COPD by pulmonary function test (odds ratio 2.1, 95% confidence interval: 1.1–3.8; P=0.019 were independently associated with colorectal malignant potential.Conclusion: The risk of colorectal malignant potential in the COPD group was higher than in the non-COPD group. We may suggest that COPD patients should consider regular colonoscopic evaluation to screen for premalignant colon polyps regardless of smoking. Keywords: COPD, colorectal adenomatous polyp, smoking, chronic obstructive pulmonary

  1. Complicações imediatas e tardias após cirurgia de reservatório ileal na polipose adenomatosa familiar Short-term and long-term postoperative complications after ileal pouch-anal anastomosis in familial adenomatous polyposis

    Raquel Franco Leal

    2008-06-01

    Full Text Available RACIONAL: A retocolectomia total com confecção de reservatório ileal é cirurgia ideal para o tratamento do cólon e reto dos doentes com polipose adenomatosa familiar, no entanto pode estar associada a complicações no pós-operatório imediato e tardio. OBJETIVO: Estudar as complicações pós-operatórias da cirurgia do reservatório ileal na polipose adenomatosa familiar. MÉTODOS: Estudo retrospectivo de 69 doentes com polipose adenomatosa familiar submetidos a cirurgia de reservatório ileal no período de 1984 a 2006, pelo Grupo de Coloproctologia da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, SP. O seguimento médio pós-operatório foi de 82 (2-280 meses. Dados de interesse: ocorrência de complicações no pós-operatório. RESULTADOS: A morbidade e mortalidade foram de 63,8% e 2,9%, respectivamente. As complicações mais freqüentes foram obstrução intestinal (17,4%, estenose da anastomose (15,9% e sepse pélvica (10,1%. Outras complicações foram isquemia aguda do reservatório ileal (4,3%, ileíte do reservatório (" pouchitis" (2,9% e fístulas relacionadas ao reservatório (2,9%. CONCLUSÕES: A morbimortalidade foi semelhante à da literatura e aceitável para uma cirurgia complexa como é a do reservatório ileal, realizada em dois tempos operatórios. A obstrução intestinal foi a complicação mais freqüente. Entretanto, isquemia do reservatório, " pouchitis" e sepse pélvica constituíram importantes complicações relacionadas à perda do reservatório ileal.BACKGROUND: Restorative proctocolectomy is the procedure of choice to treat familial adenomatous polyposis, however it can be associated to short-term and long-term postoperative complications. AIM: To evaluate the occurrence of complications related to the surgical treatment of familial adenomatous polyposis with ileal pouch technique. METHODS: Retrospective study of 69 patients with familial adenomatous polyposis after rectocolectomy

  2. Frequency of fungal infection in the nasal polyposis patients undergoing polypectomy in a tertiary care unit

    Objective: To determine the frequency of fungal infection in nasal polyposis patients undergoing polypectomy in a tertiary care ENT unit. Methodology: This cross sectional study was conducted in the department of ENT, Pakistan Institute of Medical Sciences, Islamabad. A total of 60 patients with nasal polyposis were enrolled. Patients who did not give consent, with sinonasal malignancy, diabetes, and pregnant or lactating women were excluded from study. All the patients were operated and specimens of polypectomies were sent to the Department of Pathology for fungal culture, direct microscopy and histopathology. Data was entered and analysed using SPSS version 20. (author)

  3. Colonoscopia com magnificação de imagem no diagnóstico de carcinoma colorretal invasivo da submucosa na polipose adenomatosa familiar Magnifying colonoscopy diagnosis of submucosal invasive colorectal carcinoma in familial adenomatous polyposis

    Cláudio TARTA

    2000-04-01

    Full Text Available O desenvolvimento da colonoscopia com magnificação de imagem possibilitou o estudo detalhado da mucosa colônica e o diagnóstico diferencial entre lesões neoplásicas e não-neoplásicas, a partir da observação dos pit patterns. Os resultados são comparáveis à estereomicroscopia, sendo possível, assim, presumir o diagnóstico histológico. Foi realizada colonoscopia com magnificação de imagem em paciente portadora de polipose adenomatosa familiar, demonstrando-se com este método, a diversidade de lesões polipóides benignas e as apresentações morfológicas do câncer colorretal precoce. Nesta paciente, a avaliação por magnificação (videocolonoscópio FUJINON 410 - CM -- 40X, combinada à cromoscopia com indigo carmine 0,4%, demonstrou ampla variedade de lesões distribuídas por todo o cólon: lesão de espalhamento lateral no ceco com padrão IIIL + IV, pólipos subpediculados e sésseis distribuídos pelo cólon com padrão tipo IIIL, pólipo subpediculado no cólon transverso com diâmetro aproximado de 2,0 cm e padrão IV + V, lesões plano-elevadas tipo IIIL e no cólon sigmóide lesão IIa + IIc, com padrão V de Kudo. A avaliação dos pit patterns de lesões no cólon transverso e sigmóide permitiu o diagnóstico endoscópico de lesão com invasão de submucosa.The development of colonoscopy with image magnification has enable to study the colonic mucosa in detail and to do differential diagnosis between neoplastic and non-neoplastic lesions from the observation of pit patterns. The results are comparable to stereomicroscopy being possible to predict the histologic diagnosis. In a patient with familial adenomatous polyposis magnifying colonoscopy was performed and this method demonstrated a wide variaton of benign polypoid lesions and the morphological features of early colorectal cancer. In this patient, the evaluation by image magnification, together with indigo carmin 0,4% chromoscopy, showed a wide variety of

  4. Galangin suppresses the proliferation of β-catenin response transcription-positive cancer cells by promoting adenomatous polyposis coli/Axin/glycogen synthase kinase-3β-independent β-catenin degradation.

    Gwak, Jungsug; Oh, Jingyo; Cho, Munju; Bae, Soo Kyung; Song, Im-Sook; Liu, Kwang-Hyeon; Jeong, Yongsu; Kim, Dong-Eun; Chung, Young-Hwa; Oh, Sangtaek

    2011-06-01

    Galangin is a naturally occurring bioflavonoid with anticancer activity against certain human cancers, yet little is known about its mechanism of action. Here, we used a chemical biology approach to reveal that galangin suppresses β-catenin response transcription (CRT), which is aberrantly up-regulated in colorectal and liver cancers, by promoting the degradation of intracellular β-catenin. Inhibition of glycogen synthase kinase-3β (GSK-3β) activity or mutation of the GSK-3β-targeted sequence from β-catenin was unable to abrogate the galangin-mediated degradation of β-catenin. In addition, galangin down-regulated the intracellular β-catenin levels in cancer cells with inactivating mutations of adenomatous polyposis coli (APC) or Axin, which are components of the β-catenin destruction complex. Galangin repressed the expression of β-catenin/T-cell factor-dependent genes, such as cyclin D1 and c-myc, and thus inhibited the proliferation of CRT-positive cancer cells. Structure-activity data indicated that the major structural requirements for galangin-mediated β-catenin degradation are hydroxyl groups at positions 3, 5, and 7. Our findings suggest that galangin exerts its anticancer activity by promoting APC/Axin/GSK-3β-independent proteasomal degradation of β-catenin. PMID:21406604

  5. Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling.

    Brauburger, Katharina; Akyildiz, Senem; Ruppert, Jan G; Graeb, Michael; Bernkopf, Dominic B; Hadjihannas, Michel V; Behrens, Jürgen

    2014-02-01

    The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade. So far, nothing has been known about the third member of the family, Amer3. Here we show that Amer3 binds to the armadillo repeat domain of APC, similarly to Amer1 and Amer2. Amer3 also binds to the Wnt pathway regulator conductin/axin2. Furthermore, we identified Amer1 as binding partner of Amer3. Whereas Amer1 and Amer2 are linked to the plasma membrane by an N-terminal membrane localization domain, Amer3 lacks this domain. Amer3 localizes to the cytoplasm and nucleus of epithelial cells, and this is dependent on specific nuclear import and export sequences. Functionally, exogenous Amer3 enhances the expression of a β-catenin/T-cell factor-dependent reporter gene, and knockdown of endogenous Amer3 reduces Wnt target gene expression in colorectal cancer cells. Thus, Amer3 acts as an activator of Wnt signalling, in contrast to Amer1 and Amer2, which are inhibitors, suggesting a nonredundant role of Amer proteins in the regulation of this pathway. Our data, together with those of previous studies, provide a comprehensive picture of similarities and differences within the Amer protein family. PMID:24251807

  6. MUTYH Associated Polyposis (MAP)

    Poulsen, Marie Louise Mølgaard; Bisgaard, M L

    2008-01-01

    MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial...... Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.Here we review research findings regarding MUTYH interactions, genotypic and phenotypic characteristics of MAP, as well as surveillance and...... treatment of the disease. The applied papers, published between 1/1 2002- 1/2 2008, were found through PubMed.The exact role of MUTYH in CRC tumorgenesis is still uncertain, although MAP tumors show distinct molecular features, including somatic G:C>T:A transversions in the APC gene. Furthermore...

  7. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish Polyposis Register

    Rebsdorf Pedersen, I; Hartvigsen, A; Fischer Hansen, B;

    1994-01-01

    Danish patients with Peutz-Jeghers syndrome are registered in the Danish Polyposis Register. We have initiated a new follow-up programme based on recent literature including our own cases. This has been adjusted to the regrowth rate of the polyps whereby patients with no symptoms and low regrowth...

  8. Carcinosarcoma with choriocarcinomatous and osteosarcomatous differentiation in a patient with juvenile polyposis syndrome

    Rafael Parra-Medina

    2015-09-01

    Full Text Available Juvenile polyposis syndrome (JPS is an infrequent autosomal dominant hereditary predisposition to the occurrence of hamartomatous polyps in the colon and rectum. We describe the case of a 12-year-old boy with JPS associated with an abdominal tumor. Histological sections of the abdominal tumor showed components of adenocarcinoma, osteosarcoma, and choriocarcinoma. Immunohistochemistry was AE1/AE3, CK7, HCG and SALL4 positive. Juvenile polyposis syndrome patients are at increased risk of colorectal adenocarcinoma. However, we present a case of an adenocarcinoma associated with other unusual components. This association has not been reported before.

  9. Colonic polyp patterns in familial polyposis.

    Bartram, C I; Thornton, A

    1984-02-01

    The diagnosis of familial polyposis depends on there being more than 100 adenomatous polyps in the large bowel. The polyps are the result of intramucosal microadenomatous growth. The age at which this occurs varies, and in the early stages of polyp development relatively few larger polyps may be seen. The numbers and size of the polyps as seen on double-contrast barium enema were compared with the macroscopic findings on the resected specimens in 27 patients with proven polyposis. Of these patients, 23 (83%) were diagnosed when polyps were first found at sigmoidoscopy. Radiologically the predominant polyp size was more than 5 mm in only four cases, 2-5 mm in 22 (81%), and less than 2 mm in one. Of the 22 with predominately 2-5 mm polyps, eight had significant numbers of nodules smaller than 2 mm and three had considerable numbers of polyps larger than 5 mm. Eleven (41%) were thought to have fewer than 70 polyps. Pathologically the nodular pattern (less than 2 mm) predominated in 11 (41%) and 14 had polyps of 2-5 mm. More than 100 polyps were present in each case, with fewer than 500 polyps in eight. In the 11 patients thought radiologically to have fewer than 70 polyps, the nodular pattern predominated in nine. In the initial stages of polyp growth, the larger polyps are less numerous, and the background nodular pattern is a useful diagnostic feature of familial polyposis. PMID:6607595

  10. Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours

    Walton, Sarah-Jane; Lewis, Amy; Jeffery, Rosemary; Thompson, Hannah; Feakins, Roger; Giannoulatou, Eleni; Yau, Christopher; Lindsay, James O.; Clark, Susan K.; Silver, Andrew

    2016-01-01

    Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3′-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted. PMID:27489864

  11. EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis

    Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors. Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC. Four previously unknown missense alterations were observed, which may be associated with the disease phenotype. Two of the changes, I361V and R568W, were identified in Finnish CRC patients, but not in over 300 Finnish familial CRC or PC patients or more than 200 population-matched healthy controls. The third change, D861N, was observed in a UK HPP patient, but not in additional 40 UK HPP patients or in 200 UK healthy controls. The fourth change R80H, originally identified in a Finnish CRC patient, was also found in 1/106 familial CRC patients and in 9/281 healthy controls and is likely to be a neutral polymorphism. We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this

  12. Hamartomatous polyposis syndromes

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus;

    2014-01-01

    -intestinal symptoms and types of cancers differs.Clinical awareness and early diagnosis of HPS is important, as affected patients and at-risk family members should be offered genetic counselling and surveillance. Surveillance in children with HPS might prevent or detect intestinal or extra-intestinal complications......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as......-intestinal cancer. The syndromes are rare and inherited in an autosomal dominant manner.The diagnosis of HPS has traditionally been based on clinical criteria, but can sometimes be difficult as the severity of symptoms range considerably from only a few symptoms to very severe cases - even within the same family...

  13. Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps.

    Cahill, R J; O'Sullivan, K R; Mathias, P M; Beattie, S.; Hamilton, H; O'Morain, C

    1993-01-01

    Colonic crypt cell proliferation is used as an indicator of risk of colorectal carcinoma. Subjects with adenomatous polyps and cancer have an increased cell proliferation and a shift of the proliferative zone towards the apex of the crypt. Epidemiological and in vitro studies have confirmed a link between vitamins A, E, C, beta-carotene, and colorectal cancer. In vitro bromodeoxyuridine immunohistochemical technique was used to assess the effect of daily oral supplementation with vitamin E (1...

  14. Cronkhite-Canada Syndrome: an unusual finding of gastro-intestinal adenomatous polyps in a syndrome characterized by hamartomatous polyps

    Flannery, Christopher M.; Lunn, John A.

    2014-01-01

    Cronkhite-Canada syndrome is a rare, hamartomatous polyposis syndrome of unknown etiology. Hamartomatous gastro-intestinal polyps, alopecia, onychodystrophy, cutaneous hyperpigmentation, abdominal pain, diarrhea, and complications of weight loss are typical of the syndrome. In this report, we describe a pathological finding of colonic adenomatous polyposis as opposed to hamartomatous polyposis. We also describe our treatment, long-term therapeutic plan, and the need for further research.

  15. Germline variants in Hamartomatous Polyposis Syndrome-associated genes from patients with one or few hamartomatous polyps

    Jelsig, Anne Marie; Brusgaard, Klaus; Hansen, Tine Plato;

    2016-01-01

    OBJECTIVE: A subgroup of patients with hamartomatous polyps in the GI tract has a hereditary Hamartomatous Polyposis Syndrome with an increased risk of cancer. The distinction between patients with one or few polyps and patients with a syndrome can be difficult. A pathogenic germline mutation can...... the clinical significance of genetic variants can be difficult to interpret. A family history of polyps, cancer, or extraintestinal findings or a minimum of 3-5 polyps seems to be relevant information to include before genetic testing....

  16. Patient accuracy of reporting on hereditary non-polyposis colorectal cancer-related malignancy in family members

    Katballe, N; Juul, Svend; Christensen, M.; Ørntoft, Torben Falck; Wikman, Friedrik; Laurberg, Søren

    2001-01-01

    BACKGROUND: The cancer family history is important in identifying individuals with hereditary non-polyposis colorectal cancer (HNPCC). The accuracy of a suspected HNPCC family history reported by patients with colorectal cancer was evaluated. METHODS: This was a prospective population-based study...... including consecutive patients with colorectal cancer. A questionnaire covering the occurrence of malignancy among relatives was completed. RESULTS: A total of 1200 patients with colorectal cancer completed the questionnaire. Fulfilment of Amsterdam criteria I or II according to the patients' reports was...... rejected in three of 14 cases (false-positive rate 21 per cent). Furthermore, seven of 18 probands whose families met the Amsterdam criteria I or II after verification were identified by further exploration in families who, according to the probands, met weaker criteria (false-negative rate 39 per cent...

  17. Hyperplastic polyposis associated with two asynchronous colon cancers

    Masaya Kurobe; Kuniko Abe; Naoe Kinoshita; Masanobu Anami; Hirotaka Tokai; Yoshinori Ryu; Chun Yang Wen; Takashi Kanematsu; Tomayoshi Hayashi

    2007-01-01

    We report a patient with hyperplastic polyposis who had two asynchronous colon cancers, a combined adenoma-hyperplastic polyp, a serrated adenoma, and tubular adenomas. Hyperplastic polyposis is thought to be a precancerous lesion; and adenocarcinoma arises from hyperplastic polyposis through the hyperplastic polyp-adenoma-carcinoma sequence. Most polyps in patients with hyperplastic polyposis present as blandlooking hyperplastic polyps, which are regarded as nonneoplastic lesions; however, the risk of malignancy should not be underestimated. In patients with multiple hyperplastic polyps, hyperplastic polyposis should be identified and followed up carefully in order to detect malignant transformation in the early stage.

  18. Streptococcus super antigen in polyp tissue of patients with nasal polyposis and chronic rhinosinusitis in comparison to normal population

    Mohammad Farhadi

    2013-11-01

    Full Text Available Background: Nasal polyp (NP is a benign mucosal mass located in both sinuses and nares which is mostly seen in association with cystic fibrosis, asthma or oversensitivity to aspirin. The prominent histological feature of NP is inflammatory cell infiltration with eosinophil predominance. Superantigens role in causing NP complications is already proven. Superantigens, which are mostly originated from Streptococci and Staphylococci, activate T cells strongly and increase the process of production and release of cytokines, and secretion of IgE from B cells, which in turn directly affects proinflammatory cells such as eosinophils, both in their tissues infiltration and functions.Methods: The samples are collected from patients referring to ENT clinic in Rasoul Akram training Hospital in Tehran after thorough clinical and paraclinical examinations. For control group the samples collected from patients undergoing rhinoplasty. All the samples kept frozen and sent to immunology lab. The DNA of the excised tissues extracted and amplified by using the superantigens specific primers and PCR product detected by gel electrophoresis. The date analyzed by using mean and SD and χ2 analytical tools.  Results: Fifteen healthy individuals, 25 patients with rhinosinusitis and 24 with polyposis entered this trial. Group A Streptococcus toxin detection was significantly more frequent in those with nasal polyp and rhinosinusitis compared to healthy individuals (P=0.001 and 0.005, respectively, but the results were almost the same for those with nasal polyp and rhinosinusitis (P=0.4.Conclusion: Streptococci may play an important role in induction or clinical exacerbation of polyposis and group A Streptococcus pyogenes exotoxin (SPEs with superantigenic effects may have a crucial role in etiology and pathogenesis of polyps with or without rhinosinusitis. It is postulated that, T cells polyclonal activation by SPEs may cause recruitment of inflammatory cells in nasal

  19. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  20. Fungal Agents as a Cause of Nasal Polyposis

    Mohammad Nejadkazem

    2015-01-01

    Full Text Available Introduction: Sinonasal polyposis is the most common tumor of nasal cavity and sinuses. Its complications are but not limited to sinusitis, breathing difficulties, hyposmia, anosmia and bone erosion.Methods and materials: A total of 98 patients with sinonasal polyposis were examined for suspicious causative fungal agent.Results: Direct microscopy and culture confirmed fungal agent in 8 patients (8.1% from which 3 cases had Alternaria spp, 1 patient Aspergillus spp, 1 patient Bipolaris spp, and 3 patients yeast.Conclusion: Fungi may be considered as a potential cause of sinonasal polyposis. Keywords: Sinonasal Polyposis, Rhinosinusitis, Fungi

  1. Appearance of attenuated intestinal polyposis during chronic non-steroidal anti-inflammatory drugs use

    Hugh; James; Freeman

    2012-01-01

    Aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) may prevent sporadic colonic neoplasia and reduce the polyp burden in familial adenomatous polyposis. A 41-year-old pharmacologist with no family history of intestinal polyps or cancer chronically consumed daily aspirin and other non-steroidal anti-inflammatory drugs for decades despite recurrent and multiple gastric ulcers. A cancerous polyp in the colon was endoscopically resected. Over the next 2 decades, almost 50 adenomatous polyps were removed from the rest of his colon and duodenum, typical of an attenuated form of adenomatous polyposis. Chronic and habitual use of aspirin or NSAIDS may have important significance in delaying the appearance of adenomas. The observations here emphasize the important implications for clinical risk assessment in screening programs designed to detect or prevent colon cancer.

  2. Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking

    Rhonda M Brand; David D Jones; Henry T Lynch; Randall E Brand; Patrice Watson; Ramesh Ashwathnayaran; Hemant K Roy

    2006-01-01

    AIM: To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer(HNPCC) patients.METHODS: Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC.RESULTS: Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P<0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P < 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P<0.05), hMLH1 smokers (P < 0.1) and hMSH2 smokers (P < 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P<0.05).Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P<0.05).CONCLUSION: CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

  3. Desmoid tumour in familial adenomatous polyposis. A review of literature

    Knudsen, Anne Louise; Bülow, Steffen

    2001-01-01

    combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasionof vital structures, and in cases of imminent bowel ischaemia or obstruction. The prognosis in mesenteric DT is serious, and improvement of the therapeutic strategy awaits current...

  4. Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

    Zhang, Junfang; Cao, Hailong; Zhang, Bing; CAO, HANWEI; Xu, Xiuqin; Ruan, Hang; Yi, Tingting; Tan, Li; Qu, Rui; Song, Gang; Wang, Bangmao; Hu, Tianhui

    2013-01-01

    As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and...

  5. Giant mediastinal thymolipoma in a patient with Gardner’s syndrome

    Pei, Guotian; Han, Yi; Zhou, Shijie; Liu, Zhidong

    2015-01-01

    Gardner’s syndrome is a hereditary disorder inherited as an autosomal dominant with high penetrance and variable expression that is caused by a mutation of the adenomatous polyposis coli gene. It is characterized by gastrointestinal polyps associated with multiple osteomas, dental anomalies, and skin and soft tissue tumors. We present a case of 30-year-old female patient with Gardner’s syndrome who presented with a giant mediastinal thymolipoma. The tumor was completely excised through a bila...

  6. Sensitivity to mitomycin-C and radiation of cells derived from patients with familial colon polyposis: an autosomal dominant hereditary disease

    This study was undertaken to investigate the sensitivity to mitomycin-C (MMC) of skin fibroblasts derived from patients with adenomatosis coli (AC), especially familial colon polyposis. The sensitivity to X rays and ultraviolet rays of AC cells cultured at RERF was similar to that of normal human diploid cells. However, there were large individual differences in sensitivity to MMC. DNA elongation in cells sensitive to MMC was found to be inhibited after MMC treatment. Sites highly sensitive to MMC were considered to be involved in the initial stages of DNA synthesis. (author)

  7. Chromosome number distribution and cellular DNA content in colorectal adenomas from polyposis and nonpolyposis patients

    Petersen, S E; Madsen, A L; Bak, Martin

    1991-01-01

    Ploidy analyses of colorectal adenomas were performed by combined flow cytometric DNA analysis of unfixed isolated nuclei and direct chromosome preparation after Colcemid incubation for 9-20 hours. Ten of 18 adenomas from nonpolyposis patients and 4 of 13 adenomas from patients with familial aden...

  8. High Quality Assessment of DNA Methylation in Archival Tissues from Colorectal Cancer Patients Using Quantitative High-Resolution Melting Analysis

    Balic, Marija; Pichler, Martin; Strutz, Jasmin; Heitzer, Ellen; Ausch, Christoph; Samonigg, Hellmut; Cote, Richard J.; Dandachi, Nadia

    2009-01-01

    High-resolution melting (HRM) analysis is a novel tool for analysis of promoter methylation. The aim of the present study was to establish and validate HRM analysis for detection of promoter methylation on archival formalin-fixed paraffin-embedded tissues from colorectal cancer patients. We first evaluated HRM assays for O6-methylguanine-DNA methyltransferase (MGMT) and adenomatous polyposis coli (APC) promoter methylation on a methylated DNA dilution matrix and DNA extracted from eight fresh...

  9. Platelet Count and Mean Platelet Volume in Patients with Nasal Polyposis

    Asli Tanrivermis Sayit

    2014-12-01

    Full Text Available Aim: Nasal polyps (NPs are the most common reason for nasal obstruction, with a prevalence of 1-4%. Although the etiology is not clearly known, chronic infections and mechanical, immunological, and biochemical factors can play a role in the etiology. Recently, mean platelet volume (MPV was recognized as a simple inflammatory marker in the inflammatory disease. In this study, we aimed to evaluate platelet (PLT and MPV in patients with NPs. Material and Method: This study included 80 histopathologically proven patients with NPs and 80 age- and sex-matched healthy subjects as controls. The Lund-Mackay staging system was used to evalute paranasal sinus CT scans, in patients with NPs, and paranasal sinus CT scores were recorded. Values of MPV, platelet (PLT, platelet crit (PCT and platelet distribution width (PDW were assessed in NP and control groups. Results: MPV and PLT values were found to be low in patients with NPs, at 8.57±1.62 fL and 259.99±62.03 x103/µL, respectively, compared with the control groups, at 8.79±1.49fL and 270.29±61.82 x103/µL. These findings were not statistically significant. PDW values were found to be slightly high in patients with NPs, at 17.1±1.36 fL, compared with the control group, at 16.78±1.04 fL (p=0.075. But PCT values were found to be low in patients with NPs, at 0.21±0.065, compared with the control group, at 0.23±0.069 (p=0.044. This finding was statistically significant. Discussion: In our study, the MPV and PLT values were lower in patients with NPs, but the difference was not statistically significant. According to our findings, the use of MPV as an inflammation marker in patients with NPs does not seem to be reliable.

  10. Rapid microsatellite analysis of paraffin embedded tumour specimens from patients with hereditary non-polyposis colorectal cancer.

    Raedle, J; Brieger, A; Trojan, J; Herrmann, G.; Zeuzem, S

    1998-01-01

    In screening for hereditary non-polyposis colorectal cancer (HNPCC)--an autosomal dominant disorder characterised by mutations in mismatch repair genes--detection of microsatellite instability is an important diagnostic criterion. The mono- or dinucleotide repeat DNA sequences are usually amplified from formalin fixed, paraffin embedded tissue by polymerase chain reaction after numerous time consuming steps including deparaffinisation, DNA extraction, and purification. A rapid single step met...

  11. SOLITARY VILLO ADENOMATOUS POLYP WITH CARCINOMATOUS CHANGES – RECTUM: A CASE REPORT

    Divvya

    2014-07-01

    Full Text Available olitary villo-adenomatous polyp in the rectum with focal dysplastic changes involving both adenomatous and villous component is very uncommon. This 60 year old male patient presented with intermittent hematochezia. Colonoscopy did not reveal any other polypoidal lesion in the colon.

  12. Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy

    Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life-threatening bleeding. (orig.)

  13. Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy

    Wanner, Matthew R.; Karmazyn, Boaz [Indiana University School of Medicine, Riley Hospital for Children, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Fan, Rong [Indiana University School of Medicine, Riley Hospital for Children, Department of Pathology and Laboratory Medicine, Indianapolis, IN (United States)

    2015-12-15

    Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life-threatening bleeding. (orig.)

  14. Glycoprotein expression by adenomatous polyps of the colon

    Roney, Celeste A.; Xie, Jianwu; Xu, Biying; Jabour, Paul; Griffiths, Gary; Summers, Ronald M.

    2008-03-01

    Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC Min). Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein α-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of α-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging.

  15. Sinonasal polyposis: investigation by direct coronal CT

    To demonstrate the typical clinical and CT features of sinonasal polyposis, we reviewed the clinical records and preoperative direct coronal CT scans of 35 patients with surgically proven disease. Symptoms included progressive nasal stuffiness (100 %), rhinorrhea (69 %), facial pain (60 %), headache (43 %) and anosmia (17 %). We found associations with rhinitis (46 %), asthma (29 %) and aspirin sensitivity (9 %). Coronal CT features included polypoid masses in the nasal cavity (91 %), partial or complete pansinus opacification (90 %), enlargement of infundibula (89 %), bony attenuation of the ethmoid trabeculae (63 %) and nasal septum (37 %), opacified ethmoid sinuses with convex lateral walls (51 %) and air-fluid levels (43 %). The latter feature correlated with symptoms and signs of acute sinusitis in only 40 % of patients. Recognition of sinonasal polyposis is important to the endoscopic surgeon since it can be the most troubling sinonasal inflammatory disease to manage due to its aggressive nature and tendency to recur despite appropriate treatment. (orig.)

  16. A case of gastric polyposis in antral area of stomach following prolonged proton-pump therapy

    Alqutub, Adel Nazmi

    2010-01-01

    Full Text Available We describe the clinical scenario of a young male with history of non ulcer dyspepsia who had endoscopic evidence of gastric polyposis in antral area. The polyps disappeared four months after proton pump inhibitors were stopped. Proton pump inhibitors have been linked to gastric fundal polyposis and not antral gland polyposis. This is the first report originating from an Asian country describing antral gland polyposis (AGPs in a patient on long-term PPI therapy with no evidence of Helicobacter pylori. A case report with brief review is presented.

  17. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

    Bin Li

    Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

  18. Successful treatment of cap polyposis with infliximab.

    Bookman, Ian D; Redston, Mark S; Greenberg, Gordon R

    2004-06-01

    Cap polyposis is a disorder characterized by bloody diarrhea with rectosigmoid polyps covered by a cap of fibropurulent exudate. The pathogenesis is unknown, but histological features suggest that mucosal prolapse may play a role. Drug therapies are usually unsuccessful, and treatment requires sigmoid resection or, if the disease recurs after initial surgical resection, panproctocolectomy. We report the case of a 36-year-old woman with characteristic clinical, endoscopic, and histological features of cap polyposis. Investigations included normal anorectal manometry and defecography, without evidence of prolapse. The patient's disease was unresponsive to treatment with mesalamine, antibiotics, lidocaine enemas, and corticosteroids. One infusion of infliximab 5 mg/kg provided dramatic symptomatic improvement but minimal endoscopic or histological change. After 4 infliximab infusions at 8-week intervals, endoscopy of the rectum and sigmoid colon was normal, and biopsies showed complete histological resolution of the inflammatory process. Well-being with normal endoscopy and histology has been maintained at 38 months, without further treatment. It was concluded that infliximab is effective therapy for cap polyposis and avoids the requirement for surgery. No clinical evidence was obtained to support mucosal prolapse as a causative factor, but the response to infliximab suggests a role for tumor necrosis factor-alpha in the pathogenesis of this disorder. PMID:15188181

  19. Prophylactic colectomy for hyperplastic polyposis.

    Doran, D

    2011-03-01

    Hyperplastic polyposis (HP) is important to recognise as it increases the risk of adenomata which may develop dysplastic change or frank adenocarcinoma. We present the case of a 58-year-old woman with HP.

  20. Adenomatous Polyps Of The Gallbladder” Adenomas oF the Gallbladder

    Attilio Maria Farinon; Antonio Pacella; Francesco Cetta; Mario Sianesi

    1991-01-01

    The finding of adenomatous polyps of the gallbladder is a rare occurrence and an unusual clinical problem. Among 2,145 patients who underwent cholecystectomy for gallbladder disease only 9 (0.4 per cent) presented with adenomatous polyps. There were 6 women and 3 men, aged 17 to 70 years. Preoperative ultrasonographic diagnosis was made in only 1 of 7 patients with gallstones, in contrast polypoid lesions within a gallbladder without stones were easily confirmed by both ultrasonography and or...

  1. Solitary Atypical Adenomatous Hyperplasia in a 12-Year-Old Girl

    Jin, Moran; Lee, Yang-Haeng; Kim, Bomi; Yoon, Young Chul; Wi, Jin Hong

    2016-01-01

    Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax.

  2. Solitary Atypical Adenomatous Hyperplasia in a 12-Year-Old Girl

    Jin, Moran; Lee, Yang-Haeng; Kim, Bomi; Yoon, Young Chul; Wi, Jin Hong

    2016-01-01

    Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax. PMID:27065090

  3. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

    Wu, T. T.; Rezai, B.; Rashid, A.; Luce, M.C.; Cayouette, M. C.; Kim, C.; Sani, N.; Mishra, L; Moskaluk, C A; Yardley, J. H.; Hamilton, S R

    1997-01-01

    Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of ...

  4. Evaluation of asthma improvement after endoscopic sinus surgery in nasal polyposis

    fariba Rezaeetalab

    2008-07-01

    Full Text Available Introduction: Asthma is characterized by airway inflammation, airway hyper responsiveness, and reversible airflow limitation. The prevalence of the disease has increased over 2 decades to approximately 5 to 10% of the population. The presence of nasal polyposis in asthma patients is associated with increase in asthma severity. We attempted to determine the efficacy of endoscopic sinus surgery in patients with asthma and nasal polyposis. Materials and Methods: We performed a prospective, cross-sectional study from 2001 until 2006. This study included 50 patients with severe persistent asthma and nasal polyposis. The severity of asthma (in NHLBI and NAPP and FEV1 before and after endoscopic nasal polypectomy was recorded. We used paired simple T test for comparation of data mean.The gathered data were analyzed with SPSS software. Results: In this study, median ages are 32.5 ± 14.3  years. Male to female is 2.3 to 1. All of patients have severe persistent asthma and nasal polyposis. From 50 patients with asthma and nasal polyposis, in 38 cases asthma severity and FEV1 were improved. (mean of  FEV1 before endoscopic  sinus polypectomy = 1.68 L ,  mean of FEV1 after endoscopic sinus polypectomy = 2.52 L.  Conclusion: Opening of upper airway and improvement of breathing through sinus endoscopy induce betterment of asthma severity, though the possibility of nasal polyposis should be investigated and treatment with endoscopic sinus surgery planned accordingly.  

  5. Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features

    Nyholm, H C; Nielsen, A L; Lyndrup, J; Norup, P; Thorpe, S M

    1992-01-01

    OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay ...

  6. Hereditary hemorrhagic telangiectasia and juvenile polyposis: an overlap of syndromes

    Poletto, Erica D.; Levin, Terry L. [Montefiore Medical Center, Department of Radiology, Bronx, NY (United States); Trinh, Angela M. [Albert Einstein College of Medicine, Bronx, NY (United States); Loizides, Anthony M. [Children' s Hospital at Montefiore, Department of Pediatric Gastroenterology, Bronx, NY (United States)

    2010-07-15

    Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu syndrome) is a syndrome characterized by multiorgan telangiectases and arteriovenous malformations. A subset of patients with a mutation in the MADH4 gene on chromosome 18 exhibits an overlapping syndrome of HHT and juvenile polyposis (JPS). We present one such family. Genetic testing is warranted when either HHT or JPS is diagnosed, as early recognition of this syndrome overlap allows appropriate management of these patients. (orig.)

  7. Effect of Helicobacter pylori eradication on gastric hyperplastic polyposis in Cowden's disease

    Hajime Isomoto; Hisashi Furusu; Ken Ohnita; Yusuke Takehara; Chun-Yang Wen; Shigeru Kohno

    2005-01-01

    A 21-year-old woman with complaints of hematochezia was diagnosed as having Cowden's disease (CD), an autosomal dominant condition characterized by multiple hamartomas, since facial papules and gingival papillomas were identified. On endoscopy, multiple hyperplastic polyps were seen in the rectum and left-side colon. There were also esophageal glycogenic acanthosis and hyperplastic polyposis in the antrum accompanied by Helicobacter pylorirelated gastritis. Although gastric hyperplastic polyposis had by no means regressed with unsuccessful first-line eradication therapy for H pylori, following cure of the infection with salvage therapy consisting of rabeprazole,amoxicillin and metronidazole, the polyposis lesions almost disappeared. Follow-up gastroscopy 2 and 3 years after cessation of the second-line eradication therapy revealed almost complete regression of the polyposis lesions with no evidence of H pylori infection. We recommend eradication treatment for CD patients with gastric hyperplastic polyps and the infection, as the occurrence of gastric carcinoma among hyperplastic polyps has been described.

  8. Duodenal polyposis secondary to portal hypertensive duodenopathy

    Ananta; Gurung; Philip; E; Jaffe; Xuchen; Zhang

    2015-01-01

    Portal hypertensive duodenopathy(PHD) is a recognized, but uncommon finding of portal hypertension in cirrhotic patients. Lesions associated with PHD include erythema, erosions, ulcers, telangiectasia, exaggerated villous pattern and duodenal varices. However, duodenal polyposis as a manifestation of PHD is rare. We report a case of a 52-year-old man who underwent esophagogastroduodenoscopy and was found with multiple small duodenal polyps ranging in size from 1-8 mm. Biopsy of the representative polyps revealed polypoid fragments of duodenal mucosa with villiform hyperplasia lined by reactive duodenal/gastric foveolar epithelium and underlying lamina propria showed proliferating ectatic and congested capillaries. The features were diagnostic of polyps arising in the setting of PHD.

  9. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis

    Gallagher, Michelle C; Phillips, Robin K S; Bülow, Steffen

    2006-01-01

    following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments in...

  10. Mutations of the adenomatous polyposis coli and p53 genes in a child with Turcot's syndrome.

    Barel, D; Cohen, I J; Mor, C; Stern, S; Shapiro, R; Shomrat, R; Galanti, Y; Legum, C; Zaizov, R; Avigad, S

    1998-10-23

    Turcot's syndrome is a rare heritable complex that is characterized by an association between a primary neuroepithelial tumor of the central nervous system and multiple colonic polyps. The aim of this study was to analyze genetic alterations in a case of Turcot's syndrome in a 10.5-year-old boy in whom a colorectal tumor developed 3.5 years following astrocytoma. An APC germline non-sense mutation at codon 1284 leading to a truncated protein was identified, as was a somatic p53 mutation in the colorectal carcinoma in exon 7, codon 244. The latter was not identified in the primary astrocytoma. However, immunohistochemistry revealed high p53 protein expression in both tumors, suggesting an additional p53 mutation in the primary astrocytic tumor. The diverse p53 mutations observed in this unique syndrome in two different sites and stages of the disease may shed light on the multistep progression of the malignant events. PMID:10397462

  11. Desmoid Tumor Associated With Familial Adenomatous Polyposis: Evaluation With 64-Detector CT Enterography

    Oktay Algin; Sehnaz Evrimler; Evrim Ozmen; Melike Metin; Osman Ersoy; Mustafa Karaoglanoglu

    2012-01-01

    Desmoid tumors (DTs) are benign tumors which are not seen very often, and most of the radiologists and clinicians do not know the characteristics of them very well. Correct and early diagnosis of DTs is important for decreasing mortality and morbidity. Computed tomography enterography (CTE) is a new modality for small bowel imaging which combines the improved spatial and temporal resolution of multidetector computed tomography (CT) with large volumes of ingested enteric contrast material to p...

  12. Familial adenomatous polyposis (FAP): genotype correlation to FAP phenotype with osteomas and sebaceous cysts

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    Gardner syndrome is characterized by the triad of colorectal adenomas, soft and hard tissue tumors. This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and...

  13. Familial Adenomatous Polyposis (FAP):Genotype Correlation to FAP Phenotype With Osteomas and Sebaceous Cysts

    Bisgaard, Marie Luise; Bülow, Steffen

    2006-01-01

    Gardner syndrome is characterized by the triad of colorectal adenomas, soft and hard tissue tumors. This disorder was regarded as a separate disease until the identification of the APC gene when it was recognized that mutations in the APC gene were the underlying cause of both Gardner syndrome and...

  14. Pathogenesis of nasal polyposis.

    Hulse, K E; Stevens, W W; Tan, B K; Schleimer, R P

    2015-02-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world-wide and is associated with high cost of management and significant morbidity. Yet, there is a lack of population-based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL-5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease. PMID:25482020

  15. F 18 FDG PET/CT Findings of Spontaneous Mesenteric Fibromatosis in a Patient with Gardner's Syndrome

    Sohn, Myung Hee; Jeong, Young Jin; Lim, Seok Tae; Kim, Dong Wook; Jeong, Hwan Jeong; Yim, Chang Yeol [Chonbuk National Univ. Medical School and Hospital, Jeonju (Korea, Republic of)

    2011-06-15

    Gardner's syndrome (GS), a variant of familial adenomatous polyposis, is an autosomal dominant disease. Originally, Gardner described a syndrome consisting of hereditary intestinal polyposis With osteomas and multiple cutaneous and subcutaneous lesions. The syndrome was later modified by the addition of other features, such as dental abnormalities, abdominal fibromatosis, and a number of malignant tumors. the principal cutaneous lesions that have been described in GS are epidermoid cysts. Other cutaneous lesions include fibromas, lipomas, leiomyomas, neurofibromas, and pigmented skin lesions. Fibromatoses are histologically benign, but locally aggressive fibrous tumors consisting of mature fibroblasts within an extensive collagen matrix. Most cases are sporadic, but there is a clear association with familial adenomatous polyposis and GS, suggesting a link with a mutation of the APC gene on chromosome 5q22. Fibromatosis occurs in 3.5%-29% of patients with GS, and is more likely to be multiple and to involve the mesentery and abdominal wall rather than being an isolated form. Clinically, fibromatosis presents as a painless firm soft tissue mass. Most cases of fibromatosis are believed to be precipitated by surgical trauma, however, a few cases of spontaneous occurrence have been reported. In our patient, no history of abdominal surgery or trauma was present. In addition, an abdominal CT obtained 2 years ago revealed no abnormality. Although the radiological features of fibromatosis on CT or MR have been described in the literature, F 18 FDG PET or PET/CT findings are rarely reported. The F 18 FDG uptake in patients with fibromatosis ranged from low to moderate grade and was generally heterogenous with a few tiny foci of relatively intense uptake or relatively homogenous. The areas of higher FDG metabolism are likely to represent more cellular and mitotically active areas. Mesenteric fibromatosis has similar findings to extra abdominal lesions.

  16. AN OVERVIEW OF SINONASAL POLYPOSIS: A PROSPECTIVE STUDY

    Kabikanta

    2016-03-01

    Full Text Available INTRODUCTION Sinonasal polyposis, one of the most common inflammatory mass lesions of the nose affecting up to 40% of the population. They present with nasal obstruction, anosmia, rhinorrhoea, post-nasal drip, and less commonly headache. Their aetiology remains unclear, but they are known to have associations with allergy, asthma, infection, fungus, cystic fibrosis, and aspirin sensitivity. Strong genetic factors are implicated in the pathogenesis of SNP, but genetic and molecular alterations required for its development and progression are still unclear. Management of SNP involves a combination of conservative treatment and surgical treatment. There is good evidence for the use of corticosteroids (systematic and topical, both as primary treatment and as postoperative prophylaxis against recurrence, but the prolonged course of the disease and adverse effect of systematic steroid limits their use. Surgical treatment has been refined significantly over the past 20 years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to 10% of patients. Over the last two decades, increasing insights in the pathophysiology of nasal polyposis opens prospective for new pharmacological treatment options, with eosinophilic inflammation, IgE, fungi and staphylococcus aureus as potential targets. A better understanding of the pathophysiology underlying the persistent inflammatory state in SNP is necessary to ultimately develop novel pharmacotherapeutic approaches. Here, we present the newer treatment options available for better control and possibly cure of the disease.

  17. Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development.

    Weren, Robbert D A; Venkatachalam, Ramprasath; Cazier, Jean-Baptiste; Farin, Henner F; Kets, C Marleen; de Voer, Richarda M; Vreede, Lilian; Verwiel, Eugène T P; van Asseldonk, Monique; Kamping, Eveline J; Kiemeney, Lambertus A; Neveling, Kornelia; Aben, Katja K H; Carvajal-Carmona, Luis; Nagtegaal, Iris D; Schackert, Hans K; Clevers, Hans; van de Wetering, Marc; Tomlinson, Ian P; Ligtenberg, Marjolijn J L; Hoogerbrugge, Nicoline; Geurts van Kessel, Ad; Kuiper, Roland P

    2015-06-01

    Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome-wide and targeted DNA copy number profiling and resequencing in early-onset and familial polyposis/CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC. PMID:25712196

  18. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis.

    Scanlan, Pauline D; Shanahan, Fergus; Clune, Yvonne; Collins, John K; O'Sullivan, Gerald C; O'Riordan, Micheal; Holmes, Elaine; Wang, Yulan; Marchesi, Julian R

    2008-03-01

    A role for the intestinal microbiota is routinely cited as a potential aetiological factor in colorectal cancer initiation and progression. As the majority of bacteria in the gut are refractory to culture we investigated this ecosystem in subjects with colorectal cancer and with adenomatous polyposis who are at high risk of developing colorectal cancer, using culture-independent methods. Twenty colorectal cancer and 20 polypectomized volunteers were chosen for this analysis. An exploration of the diversity and temporal stability of the dominant bacteria and several bacterial subgroups was undertaken using 16S rRNA gene denaturing gradient gel electrophoresis and ribosomal intergenic spacer analysis (RISA). Metabonomic analysis of the distal gut microbiota's environment was also undertaken. A significantly reduced temporal stability and increased diversity for the microbiota of subjects with colorectal cancer and polyposis was evident. A significantly increased diversity of the Clostridium leptum and C. coccoides subgroups was also noted for both disease groups. A clear division in the metabonome was observed for the colorectal cancer and polypectomized subjects compared with control volunteers. The intestinal microbiota and their metabolites are significantly altered in both colorectal cancer and polypectomized subjects compared with controls. PMID:18237311

  19. Decreased Expression of FOXP3 in Nasal Polyposis

    Roongrotwattanasiri, Kannika; Pawankar, Ruby; KIMURA, SATOKO; Mori, Sachiko; Nonaka, Manabu; Yagi, Toshiaki

    2011-01-01

    Purpose The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulator...

  20. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen; Svendsen, L B; Søndergaard, J O; Bülow, Steffen

    1997-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...

  1. Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais Cytokine profile in subjects with Cystic Fibrosis and nasal polyposis compared to patients with no nasal disorders

    Flávio Barbosa Nunes

    2010-02-01

    Full Text Available Embora o perfil das citocinas na polipose nasossinusal seja bem documentado, pouco se sabe sobre estas proteínas quando associadas à Fibrose Cística. OBJETIVOS: Avaliar a expressão das citocinas IL¬4, IL¬5, IL¬6, IL¬8, GM¬C-SF e IFN--y analisada pela RT¬-PCR, nos pólipos de pacientes com Fibrose Cística. MATERIAL E MÉTODO: Estudo transversal, prospectivo, de 24 pacientes, 13 com Fibrose Cística e polipose nasossinusal (Grupo Fibrose Cística e 11 com exame otorrinolaringológico normal (Grupo Controle. A média de idade foi de 21 anos (3¬-57, 12 eram do sexo masculino e 12 do sexo feminino. O perfil das citocinas foi pesquisado nos fragmentos de mucosa (Grupo Controle ou pólipo nasal (Grupo Fibrose Cística através da RT-¬PCR. Foram estudadas as transcrições para as citocinas IL¬4, IL¬5, IL¬6, IL¬8, IFN¬y e GM¬-CSF ajustadas pelo valor da β¬ actina. RESULTADOS: As interleucinas 5, 6, 8 e GM¬-CSF foram semelhantes nos dois grupos (p>0,05. Menores valores de IFNy¬ (p=0,03 e forte tendência de aumento de IL¬4 (p=0,06 foram observados no grupo Fibrose Cística. CONCLUSÃO: As células inflamatórias e estruturais podem produzir RNA mensageiro para IL¬4, bloqueando a produção de outras citocinas com IFN-y¬, sugerindo a participação destes mecanismos na formação dos pólipos da Fibrose Cística.Although the cytokine profile in nasal polyposis is well documented, little is known about cytokines associated to cystic fibrosis. AIM: Assess the expression of cytokines IL¬4, IL¬5, IL¬6, IL¬8, GM¬-CSF and IFN¬-y, analyzed through RT-PCR, in the polyps of patients with cystic fibrosis. MATERIALS AND METHODS: A cross-sectional, prospective study was carried out with 24 patients, 13 of whom had cystic fibrosis and nasal polyposis (Cystic Fibrosis Group and 11 had normal otorhinolaryngological exams (Control Group. The average age was 21 years (3¬57; 12 participants were males and 12 were females. The cytokine

  2. Clinicopathologic Analysis of 2,889 Nanchang-Area Patients with Colorectal Polyps

    Guohua Li; Wangdi Liao; Ping Xu; Nonghua Lv; Chongwen Wang

    2007-01-01

    OBJECTIVE To study the clinicopathologic characteristics.changes in the nature and incidence of colorectal polyps in the Nanchang area,Jiangxi,Province.METHODS We retrospectively investigated the patients with colorectal polyps who were diagnosed by colonoscopy and pathology in our hospital from 1990 to 2004.The analysis involved the incidence,average patient age,polyp location and pathological types.We recorded the changes of the polyp clinicopathologic features by comparing the clinicopathologic types of colorectal polyps over five-year periods.RESULTS Of the 21,853 patients who received a colonoscopy,2,889(13.2%) were diagnosed with colorectal polyps.Their average age was 46.6±16.5 years,with a male to female ratio of 1.8:1.The males were older than females (47.1±17.5 vs.45.5±14.5.P<0.05).Location of the polyps:41% in the rectum.27-7% in the sigmoid colon.35.8% in the left side verus 23.1% in the right side (P<0.05).Patients with polyps located in the transverse and ascending colon were older than those with polyps in the rectum and sigmoid colon (P<O.05).Adenomatous polyps comprised the most common type (67%) and the rectum was the most common site for each type,especially juvenile and retention polyps.Juvenile polyps were found in the youngest patients (12±4.8,P<0.05)and the adenomatous in the oldest(52±14,P<0.05).The ratio of patients with polyposis comprised 1.2%.and patients with polyps accompanied with colorectal cancer comprised 6.1%.Examination of the changes in the incidence,the average patient age,and adenomatous type showed that they had all increased.but the frequency of inflammatory and retention polyps decreased.CONCLUSIoN Colorectal polyps are a common problem.The frequency iS greater in males compared to females and the rectum and sigmoid colon had the highest incidence.Most iuvenile and retention polyps were found in young patients.but most adenomatous occurred in adults.In recent years,the incidence of colorectal polyps

  3. Infection and HLA-G Molecules in Nasal Polyposis

    Rizzo, Roberta; Malagutti, Nicola; Bortolotti, Daria; Gentili, Valentina; Rotola, Antonella; Fainardi, Enrico; Pezzolo, Teresa; Aimoni, Claudia; Pelucchi, Stefano; Di Luca, Dario; Pastore, Antonio

    2014-01-01

    Sinonasal polyposis (SNP) is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV) infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD), 10 patients with SNP and suffering from allergic diseases (SNP-WAD), and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G) and IL-10 receptor (IL-10R) and of soluble HLA-G (sHLA-G) and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5), all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD. PMID:24741599

  4. Infection and HLA-G Molecules in Nasal Polyposis

    Roberta Rizzo

    2014-01-01

    Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

  5. [Hereditary non-polyposis colorectal cancer. Report of four siblings].

    Zárate, Alejandro; Alvarez, Karin; Wielandt, Ana María; Hevia, Montserrat; De la Fuente, Marjorie; Carvallo, Pilar; López-Köstner, Francisco

    2008-06-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene. PMID:18769833

  6. Serrated polyposis syndrome: Molecular, pathological and clinical aspects

    Carla Guarinos; Cristina Sánchez-Fortún; María Rodríguez-Soler; Cristina Alenda; Artemio Payá; Rodrigo Jover

    2012-01-01

    Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found that this pathway accounts for only approximately 70%-80%of colorectal cancer (CRC) cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

  7. Uso de analgésicos e antiinflamatórios em pacientes portadores de polipose nasossinusal eosinofílica tolerantes e intolerantes à aspirina Use of analgesics and anti-inflammatory drugs in patients with eosinophilic nasal polyposis tolerant and intolerant to aspirin

    Helena M. G. Becker

    2003-06-01

    dipirona e ao álcool, respectivamente, em quase metade e um terço destes pacientes.Following aspirin introduction as medicine, several reports were described concerning adverse reactions after its ingestion. Widal et al. (1922¹ were the first investigators to associate Aspirin intolerance (AI with asthma and nasal polyps (NP followed by Samter & Beers (1967². Such intolerance was manifested mainly by nasal obstruction and/or bronchospasm related to the cyclooxygenase-1 (COX-1 inhibition and consequent overproduction of leukotrienes. This might also be triggered by the administration of other non-steroid anti-inflammatory drugs, acetaminophen, food dyes and additives and alcohol. AIM: To analyze the risks of the analgesics and anti-inflammatory drugs use in patients with eosinophilic nasal polyposis tolerant and intolerant to aspirin. STUDY DESIGN: Transversal cohort study. MATERIAL AND METHOD: 45 patients were selected # 15 suffering from eosinophilic nasosinusal polyposis, tolerant to aspirin (group TA; other 15 with eosinophilic nasosinusal polyposis associated with aspirin intolerance (group AI, and 15 patients without nasosinusal polyposis with septal deviation (control group. The presence of reaction to aspirin, dipyrone, acetaminophen, other non-steroids anti-inflammatory drugs, food dyes and additives, other drugs or chemical substances was detected by inquiry. To exclude aspirin intolerance in TA and control groups, oral provocation test with aspirin was carried out. RESULTS: Bronchospasm was the main aspirin reaction in patients suffering from eosinophilic nasosinusal polyposis and which also showed with ingestion of acetaminophen (20%, alcohol (27%, non-steroids anti-inflammatory drugs (60% and dipyrone (47%. CONCLUSION: In patients with eosinophilic nasosinusal polyposis associated with aspirin intolerance it is important to do the diagnosis of intolerance to other drugs. The use of dipyrone and alcohol is worth attention, once its intolerance was observed

  8. Comorbidities in Severe Asthma: Frequency of Rhinitis, Nasal Polyposis, Gastroesophageal Reflux Disease, Vocal Cord Dysfunction and Bronchiectasis

    Carla Bisaccioni; Marcelo Vivolo Aun; Edcarlos Cajuela; Jorge Kalil; Rosana Câmara Agondi; Pedro Giavina-Bianchi

    2009-01-01

    OBJECTIVES: Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD), nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 20...

  9. p53 Nuclear Accumulation and Bcl-2 Expression in Contiguous Adenomatous Components of Colorectal Adenocarcinomas Predict Aggressive Tumor Behavior

    Shanmugam, Chandrakumar; Katkoori, Venkat R.; Jhala, Nirag C.; Grizzle, William E.; Gene P Siegal; Manne, Upender

    2008-01-01

    For subsets of colorectal adenocarcinoma (CRC) patients, nuclear accumulation of p53 (p53nac) and Bcl-2 expression are prognostic indicators. To understand their role in the progression of CRC we evaluated 90 CRCs and their contiguous adenomatous components (CAdCs) for immunohistochemical expression of these markers. In general, p53nac and Bcl-2 expression was significantly increased when comparing normal colonic epithelia to CAdCs and CRCs. Thirteen (14%) CAdCs that demonstrated p53nac conti...

  10. Is epidermal growth factor involved in development of duodenal polyps in familial polyposis coli?

    Poulsen, Steen Seier

    1988-01-01

    Duodenal adenomas are a frequent extracolonic manifestation in patients with familial polyposis coli (FPC). Epidermal growth factor (EGF), a polypeptide that stimulates cellular growth and differentiation, is localized in Paneth cells in the small intestine. In two patients with FPC, we found EGF...... immunoreactivity in duodenal adenomas. Numerous EGF immunoreactive Paneth cells were localized, not as usually, in the bottom of the crypts, but scattered along the crypts alone or in clusters. We do not know whether EGF is involved in the development of duodenal polyps in FPC patients, or whether the present...... findings represent secondary changes in duodenal polyps....

  11. Familiær adenomatøs polypose

    Bülow, Steffen

    2013-01-01

    identification of gene carriers by DNA analysis or endoscopy the prognosis is good after early colectomy, but life-long surveillance of the rectum and the duodenum is necessary. The Danish Polyposis Register coordinates prophylactic examination and treatment in the families, and serves as basis for research....

  12. Local IgE production in nonatopic nasal polyposis.

    Sheahan, Patrick

    2012-02-01

    INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. METHODS: Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. RESULTS: Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). CONCLUSIONS: Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy.

  13. Pathogenesis and management of nasal polyposis in cystic fibrosis.

    Mainz, Jochen G; Koitschev, Assen

    2012-04-01

    Beginning in preschool age, during their lives, upto 50% of cystic fibrosis (CF) patients experience obstructing nasal polyposis (NP), which is rare in non-CF children. Pathogenetic factors of NP in general and especially in CF are still obscure. However, defective epithelial ion transport from mucosal glands plays a central role in CF, and viscous secretions impair mucociliary clearance, promoting chronic pathogen colonization and neutrophil-dominated chronic inflammation.Presently, CF-NP is not curable but can be clinically stabilized,though the large variety of proposed treatment modalities indicates a lack of standardization and of evidence of treatment efficacy. When conservative measures are exhausted, surgical intervention combining individually adapted endoscopic sinus surgery and supportive conservative treatment is performed. Topical steroids, approved as the gold standard for non-CF NP, may be beneficial, but they are discussed to be less effective in neutrophilic inflammation,and CF-specific antimicrobial and mucolytic therapy, as is true of all treatment modalities, urgently requires evaluation by controlled clinical trials within interdisciplinary networks. PMID:23520643

  14. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  15. Mutator gene and hereditary non-polyposis colorectal cancer

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  16. The incidence of postoperative venous thrombosis among patients with ulcerative colitis.

    O'Connor, O J

    2012-02-03

    BACKGROUND: Patients with Ulcerative Colitis (UC) have inherent prothrombotic tendencies. It is unknown whether this necessitates the use of additional perioperative anti-thrombotic prophylaxis when such patients require major surgery. METHODS: The postoperative courses of 79 patients with UC undergoing 180 major abdominal and pelvic operations were examined for clinical and radiological evidence of venous thrombosis. Eighteen patients with Familial Adenomatous Polyposis (FAP) having surgery (35 operations) of similar magnitude were also studied. Standard anti-thrombosis prophylaxis was utilised in all patients. RESULTS: Nine patients with UC were clinically suspected of developing postoperative venous thrombosis, but only three (3.8%) had their diagnosis confirmed radiologically (all had a pulmonary embolus). Therefore, the overall postoperative thrombosis rate, on an intention to treat basis, was 1.7% (3\\/180). No patient with FAP developed significant venous thrombosis. CONCLUSION: Standard perioperative antithrombotic modalities are sufficient to maintain any potential increase in postoperative thrombotic risk at an acceptable level in patients with UC undergoing operative intervention.

  17. The benefits of a laparoscopic approach in ileal pouch anal anastomosis formation: a single institutional retrospective case-matched experience.

    Kelly, J

    2010-06-01

    A laparoscopic approach to ileoanal pouch formation is novel. By using prospectively gathered data, laparoscopic and open restorative proctocolectomy procedures in mucosal ulcerative colitis (UC) and familial adenomatous polyposis (FAP) patients were compared using a case-matched design.

  18. Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis

    Carla Bisaccioni

    2009-01-01

    Full Text Available OBJECTIVES: Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD, nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis. RESULTS: We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4%; 18 (7.3% had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3% had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6% patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6% patients. Vocal cord dysfunction was suspected in 16 (6.5% and confirmed through laryngoscopy in 4 (1.6%. The patient records provided CT scans of the chest for 105 patients, and 26 (24.8% showed bronchiectasis. DISCUSSION: Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.

  19. Changes in the absorption of bile acids after total colectomy in patients with an ileostomy or pouch-anal anastomosis

    Bile acid absorption was investigated using 75Se Taurohomocholate (SeHCAT) in controls and patients who had undergone total colectomy with either conventional ileostomy or pouch-anal anastomosis for ulcerative colitis or adenomatous polyposis. Whole-body retention of SeHCAT after 168 hours was greater in the controls than the patients who had undergone colectomy (P less than .05). Retention of SeHCAT did not differ significantly between patients with an ileostomy and patients with pouch-anal anastomosis, but patients with an ileostomy and ileal resection of more than 20 cm retained less SeHCAT than patients with a pouch-anal anastomosis (P less than .01). Analysis of fecal bile acids from ileostomies and pouches showed that bacterial metabolism of primary conjugated bile acids was greater in patients with a pouch. It was concluded that bile acid absorption was not significantly impaired by construction of a pouch compared with conventional ileostomy, but bacterial metabolism of bile acids was greater in the pouches

  20. The differentiation and prognostic implication of the solitary colonic polyp and the polyposis syndromes: A radiologic, histologic, and pathologic approach

    The differential diagnosis of the solitary colonic polyp and the implications and prognostic significance of the solitary colonic polyp and the polyposis syndromes are frequently confusing because of imprecise and overlapping terminology. Such confusion may lead to misdiagnosis or overdiagnosis and improper patient treatment and surveillance. In the first part of this course, basic terms are defined to acquaint all participants with current common ground. The most frequently occurring solitary polyps (e.g., the colonic adenoma, hyperplastic polyp, Peutz-Jeghers hamartoma, juvenile hamartoma, and inflammatory polyp) are illustrated in detail with radiologic-histologic-pathologic correlation. The prognostic significance of each type of lesion and a scheme for proper colonic surveillance is discussed. In the second part of the session, there is a thorough discussion of multiple colonic polyps and the polyposis syndromes. Radiologic-pathologic correlation are used to illustrate these entities, and therapeutic and diagnostic implications are thoroughly covered. The differential diagnosis of the polyposis syndromes, including lymphoid abnormalities, pneumatosis intestinalis, and colitis cystica profunda, are mentioned. The participant should expect to gain a full understanding of the solitary and multiple colonic polyp states and algorithms for prognosis and treatment

  1. A case of cap polyposis remission by betamethasone enema after antibiotics therapy including Helicobacter pylori eradication.

    Suzuki, Hideo; Sato, Masashi; Akutsu, Daisuke; Sugiyama, Hiroaki; Sato, Taiki; Mizokami, Yuji

    2014-06-01

    We report the case of a 58-year-old woman who was referred to our hospital due to frequent bloody mucus diarrhea. She was diagnosed with cap polyposis based on typical endoscopic and histological findings. Colonoscopy revealed multiple, reddish, mucus-capped polypoid lesions from the rectum to the sigmoid colon. A pathological examination revealed that the polyps were covered by erosive and inflamed granulation tissue with decreased crypt cells. Laboratory data indicated positive values for Helicobacter pylori immunoglobulin G antibody and hypoproteinemia. Metronidazole, H. pylori eradication, and levofloxacin therapies were not effective; however, the subsequent administration of betamethasone enema dramatically improved the clinical symptoms and endoscopic findings. The hypoproteinemia was normalized after the therapy. The dose of the betamethasone enema was tapered gradually, and no recurrence was observed 6 months after discontinuation of the treatment. This case suggests that betamethasone enema may be considered as the second treatment choice for cap polyposis patients after H. pylori eradication, metronidazole or levofloxacin therapy. PMID:24949613

  2. [Juvenile recto-colonic polyposis. Apropos of a case in Madagascar].

    Alandry, G; Le Quellec, B; Philippon, G; Gouot, E; Ribault, L

    1987-01-01

    The authors relate the first case of juvenile polyposis coli noticed in Madagascar. It is a sporadic case developing a serious clinic picture with an accidentally fatal end in a 7 years old Malagasy girl. They recall the principal epidemiological, anatomopathological, clinic and evolutive features which are typical of this polyposis. They wish that the way to medical progress will soon lead to better knowledge of the place of the intestinal polyposis in African countries. PMID:3586969

  3. Segmental resection with primary anastomosis is not always safe in splenic flexure perforation

    Weledji, Elroy P; Mokake, Martin D.; Sinju, Motaze

    2016-01-01

    Background Familial adenomatous polyposis (FAP) is caused by a rare mutation of the adenomatous polyposis coli gene on Chromosome 5q. The risk of colorectal cancer in patients with FAP is nearly 100 % and intensive endoscopic surveillance or prophylactic colectomy are mandatory. If extensive endoscopic surveillance is chosen, there is a cumulative risk of perforation and bleeding especially after polypectomy. We discussed the problems and options in the management of the late diagnosis of an ...

  4. Contralateral recurrence of aggressive fibromatosis in a young woman: A case report and review of the literature

    SCHMOYER, CHRISTOPHER J.; Brereton, Harmar D; BLOMAIN, ERIC W.

    2015-01-01

    Aggressive fibromatosis (AF) is a benign non-encapsulated tumor of mesenchymal origin, with a tendency for local spread along fascial planes. Local invasion can lead to extensive morbidity and even mortality due to destruction of the bones, organs and soft tissues. This rare lesion is observed 1,000 times more frequently in patients with familial adenomatous polyposis or Gardner's syndrome due to the inheritance of the adenomatous polyposis coli (APC) gene. While AF does not metastasize, loca...

  5. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis

  6. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    Tops Carli MJ

    2009-06-01

    Full Text Available Abstract Background MUTYH-associated polyposis (MAP is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC. Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. Methods From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR of APC, p53, and SMAD4 were analyzed for somatic mutations. Results MAP CRCs frequently localized to the proximal colon (69%, 40/58, were mucinous in 21% (9/42, and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40; all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36 while 64% (23/36 had KRAS2 mutations (22/23 c.34G>T. G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. Conclusion MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development but not in P53 and SMAD4 (implicated in tumour progression might indicate a predominant MUTYH effect in early carcinogenesis.

  7. Germline Mutations in the Polyposis-Associated Genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 Are Not Common in Individuals with Serrated Polyposis Syndrome.

    Mark Clendenning

    Full Text Available Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS, are among those who carry germline mutations in genes associated with polyposis syndromes including; (1 genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN, (2 MUTYH-associated polyposis and (3 GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS. The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes.A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3, were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C and 13 (G396D, and for the duplication upstream of GREM1.We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1.Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.

  8. The challenge of extraabdominal desmoid tumour management in patients with Gardner's syndrome: radiofrequency ablation, a promising option.

    Cobianchi, Lorenzo; Ravetta, Valentina; Viera, Francesca Torello; Filisetti, Claudia; Siri, Barbara; Segalini, Edoardo; Maestri, Marcello; Dominioni, Tommaso; Alessiani, Mario; Rossi, Sandro; Dionigi, Paolo

    2014-01-01

    Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner's syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner's syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner's syndrome. PMID:25429890

  9. Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia

    Richard Siderits; Iman Hanna; Zahid Baig; Janusz J Godyn

    2006-01-01

    A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric (EG) junction and grade Ⅰ erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and NSE were positive.This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type Ⅱb (MEN Ⅱb). Iansoprazole (Prevacid)was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild nonspecific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease (GERD) and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient's reflux.

  10. A typical adenomatous hyperplasia of the lung: correlation of radiographic and pathologic findings

    Objective: To study radiographic features of atypical adenomatous hyperplasia (AAH) of lung and correlate them with their pathologic findings, so as to improve the imaging diagnose. Methods: The imaging features of 8 patients with pathology- proved AAH were reviewed. All patients were women with age ranging from 35 to 74 years. All cases had chest radiography and HRCT. The radiographic findings were studied retrospectively and correlated with those of pat hology. Results: On chest X-ray, the foci in five patients presented as nodule-like area of a bit high attenuation, while the chest radiograph in the other three patients were negative. On HRCT, all 8 patients presented as non-solid nodules. All lesions were round or oval shaped with well-defined margin (n=4) or poor-defined margin (n=3). The greatest dimension of the lesions ranged from 5.0 mm to 20.0 mm. Their CT value ranged from -362.7 HU to -485.6 HU, the mean CT value was (-423.0 ± 47.0) HU. Air bronchograms and/or bubbles were seen in 5 lesions. Coarse spiculation and pleural tag was not seen in any lesion. Before operation, all the nodules did not change in size over a follow-up period from one month to six months. Pathologic findings showed atypical epithelial cell proliferation along thickened alveolar septa without alveolar collapse. Conclusion: AAH should be considered in cases with the following features: (1) nodules ate found in lung cancer screening or incidentally detected; (2) the diameter of the nodule is usually less than 10 mm; (3) the lesion presented as non-solid nodule on HRCT, air bronchogram and/or bubble sign can be seen; (4) no coarse spiculation and plural tag was seen. (authors)

  11. Analysis of mtDNA sequence variants in colorectal adenomatous polyps

    Grizzle William

    2010-10-01

    Full Text Available Abstract Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57% variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17 in tubular and 57% (13/23 in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was

  12. Manifestations of juvenile polyposis syndrome in SMAD4 mutation carriers of a kindred.

    Schwetz, Verena; Uhrig, Sabine; Spuller, Ekkehard; Deutschmann, Andrea; Högenauer, Christoph

    2012-08-01

    The autosomal dominantly inherited juvenile polyposis syndrome (JPS) leads to the development of multiple hamartomatous polyps in the gastrointestinal tract and is a precancerous condition. In a large family with a newly identified SMAD4 mutation (c.543delC), we describe the clinical manifestations of JPS. Nine affected SMAD4 mutation-positive family members were screened and treated for manifestations of JPS. Two family members were symptomatic at the time of diagnosis; seven were asymptomatic - independent of the severity of the manifestation. Each mutation carrier presented with colonic juvenile polyps, seven out of nine with additional gastric manifestations. One asymptomatic patient had early gastric cancer; another patient had a villous adenoma with high-grade intraepithelial neoplasia in the colon. Three patients had biliary lesions including a bile duct hamartoma in one and gallbladder polyps in two. Three patients had gastrointestinal vascular malformations. All mutation carriers were affected by JPS. Interestingly, the manifestations and their severity differed considerably between the patients, suggesting secondary factors influencing JPS manifestations such as Helicobacter pylori infection. PMID:22617360

  13. Hamartomatous gastric polyposis in a patient with tuberous sclerosis.

    Kim, B. K.; Kim, Y. I.; Kim, W. H.

    2000-01-01

    A 42-year-old female diagnosed with tuberous sclerosis was found to have multiple polyps in the fundus of stomach. On histologic examination, the lesions were hamartomatous polyps. In tuberous sclerosis, many lesions occur in multiple organs and there are several reports about the frequent association of hamartomatous polyps of the colon. However, gastric manifestation of tuberous sclerosis has not been established probably due to its asymptomatic nature. This is the first report of multiple ...

  14. A Rare Case of Aggressive Fibromatosis Infiltrating Dorsal Muscles in a 6-Year-Old Patient – CT, MRI and Elastography Evaluation

    The term fibromatosis or desmoid tumor refers to a group of benign fibrous growths without metastatic potential but with a significant risk of local recurrence. These lesions typically present infiltrative growth pattern with local invasion of adjacent tissues. This tendency is the reason for a relatively high rate of local recurrence, even after surgical removal. Fibromatosis is a very rare condition in general population but occurs more frequently in one of the familial cancer predispositions known as familial adenomatous polyposis (FAP) or Gardner syndrome. There are two main groups of fibromatosis: superficial (small, slow-growing lesions) and deep, also known as aggressive fibromatosis (large, rapid-growing lesions). We report a case of a 6-year-old boy suffering from an aggressive form of fibromatosis. The patient developed a large pathological mass extending from the neck to the loins. After incisional biopsy and histpoathological examination of the sample, a diagnosis of aggressive fibromatosis was established. During the whole diagnostic process, different imaging techniques including CT, MRI and sonoelastography were used. As the surgical treatment was not possible, the patient was finally qualified for chemotherapy. Eventual diagnosis of aggressive fibromatosis is based on histopathological examination. However, it is an important condition that should be included in differential diagnosis of soft-tissue masses found in diagnostic imaging. Radiologists should be careful especially in defining the margins of infiltration in case of potential surgical treatment

  15. Multiple lymphomatous polyposis of the gastrointestinal tract ; report of three cases

    In 1961, Cornes first introduced the term multiple lymphomatous polyposis (MLP), and since then, this very rare disease has been considered as a malignant lymphoma originating in the mantle zone of gastrointestinal lymphoid tissue. MLP presents with a 0.5-2.0 cm sized polypoid tumor, which affects long segments of the alimentary tract and frequently invades the mesenteric lymph nodes. It often consists of a dominant mass rather than polyps. We describe three cases of endoscopically proven multiple lymphomatous polyposis, and include a review of the literature. In differentiating multiple lymphomatous polyposis and other types of multiple polyposis in the gastrointestinal tract, the following features are helpful : the smooth surface of polyps, which is similar to a gem seen during a barium examination; the typical appearance of a gastric submucosal tumor and hypertrophied gastric mucosal folds in UGI; the presence of enlarged lymph nodes, as seen on abdominal CT scanning. (author). 9 refs., 2 tabs., 3 figs

  16. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  17. Lynch syndrome (hereditary non-polyposis colorectal cancer): current concepts and approaches to management.

    Ricciardiello, Luigi; Boland, C Richard

    2005-10-01

    Colorectal cancer is among the most frequent causes of cancer death worldwide. An inherited predisposition to cancer of the colon and other organs, Lynch syndrome-- also called hereditary non-polyposis colorectal cancer--is probably the most frequent cause of hereditary cancer and is often found in a colon cancer patient and traced through other family members. However, this syndrome is not only characterized by the early onset of colon cancers but also by a predisposition to a constellation of extraintestinal cancers that tend to be misdiagnosed. With new diagnostic technologies, the incidence of familial/inherited versus sporadic cases may appear to increase, due to the recognition of cancers in families that do not fulfill clinical guidelines developed prior to knowledge of the genetic basis of this disease. We now have the ability and the responsibility to detect and prevent this disease, and equally important, to direct patients to specifically targeted treatment. Specialists should be aware of the significance of inherited colon cancer and should become familiar with the molecular diagnostic tests now widely available. PMID:16168241

  18. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  19. Disease: H01025 [KEGG MEDICUS

    Full Text Available tosomal dominantly inherited disorder characterized by the early onset of hundreds to thousands of adenomas throughou... polyposis coli (APC) gene. In a subset of individuals, a MUTYH mutation causes a reces...Rozen P Familial adenomatous polyposis. Orphanet J Rare Dis 4:22 (2009) PMID:21884696 (des...H01025 Familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an au...fter the appearance of the polyps. The genetic defect in FAP is a germline mutation in the adenomatous

  20. Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis: Relationship with colonic metaplasia

    Livia Biancone; Francesco Pallone; Emma Calabrese; Giampiero Palmieri; Carmelina Petruzziello; Sara Onali; Giuseppe Sigismondo Sica; Marta Cossignani; Giovanna Condino; Kiron Moy Das

    2008-01-01

    AIM:To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA),ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium.METHODS:A total of 19 patients with IRA under regular follow up were enrolled,including 11.UC and 8 controls (6 Crohn's disease,CD;1 familial adenomatous polyposis,FAP;1 colon cancer,colon K).Ileal lesions were identified by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump.Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5,hTMS (CG3).Possible relation between development of colonic metaplasia and ileal lesions was investigated.RESULTS:Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient.The neo-terminal ileum was therefore investigated in 10/11 UC patients.Ileal ulcers were detected in 7/10 UC,associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC.In controls,recurrence occurred in 4/6 CD,associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3.CONCLUSION:Present findings suggest that in UC,ileal lesions associated with changes towards colonic epithelium may develop also after IRA.Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia,leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.

  1. Bmp signaling in colonic mesenchyme regulates stromal microenvironment and protects from polyposis initiation.

    Allaire, Joannie M; Roy, Sébastien A B; Ouellet, Camille; Lemieux, Étienne; Jones, Christine; Paquet, Marilène; Boudreau, Francois; Perreault, Nathalie

    2016-06-01

    In the colon, myofibroblasts are primary contributors in the establishment of the microenvironment involved in tissue homeostasis. Alterations in myofibroblast functions lead to changes resulting in a toxic microenvironment nurturing tumorigenesis. Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in adult gut homeostasis. Studies in genetically-modified mice have shown that Bmp disruption in all cell layers leads to the development of gut polyposis. In contrast, our studies showed that loss of Bmp exclusively in the gastrointestinal epithelium resulted in increased epithelial proliferation without polyposis initiation, thus suggesting a key role for mesenchymal Bmp signaling in polyposis initiation. In order to identify the role of mesenchymal Bmp signaling on the microenvironment and its impact on colonic mucosa, a mouse model was generated with suppression of Bmp signaling exclusively in myofibroblasts (Bmpr1aΔMES). Bmpr1aΔMES mice exhibited increased subepithelial proliferation with changes in cellular composition leading to the development of a primed stroma with modulation of extracellular matrix proteins, immune cells and cytokines as early as 90 days of age. This microenvironmental deregulation was associated with increased polyposis initiation at one year of age. These results are the first to demonstrate that mesenchymal Bmpr1a inactivation alone is sufficient to prompt an expansion of myofibroblasts leading to the development of a reactive mesenchyme that contributes to polyposis initiation in the colon. These findings support the novel concept that inhibition of Bmp signaling in mesenchymal cells surrounding the normal epithelium leads to important changes instructing a toxic microenvironment sufficient to induce colonic polyposis. PMID:26773796

  2. High-resolution CT findings of pulmonary atypical adenomatous hyperplasia of 5 mm or less in diameter

    The objective of this study was to clarify the high-resolution CT (HRCT) findings of pulmonary atypical adenomatous hyperplasia (AAH) of 5 mm or less in diameter. We evaluated the HRCT findings of 43 histopathologically confirmed AAH of 5 mm or less in diameter in 7 patients who underwent lobectomy for pulmonary adenocarcinoma. For comparison, we also examined the HRCT findings of 13 bronchioloalveolar carcinomas (BAC) of the same size from these patients. We identified 36 of 43 AAH and all 13 BAC on HRCT performed with multidetector-row CT. Thirty-five AAH and 11 BAC showed ground-glass opacity without any high-attenuation component. Margins of 20 AAH were well defined, and 16 were ill defined. In BAC, 11 lesions demonstrated well-defined margins, with only 2 showing ill-defined margins. Most AAH lesions of 5 mm or less in diameter are identified as ground-glass opacity on HRCT. Detection of minute ground-glass opacity is important in locating AAH on HRCT. (author)

  3. A rare case of asymptomatic radioiodine-avid renal and brain metastases 20 years after hemi-thyroidectomy for adenomatous goiter

    Santhosh, Sampath; Bhattacharya, Anish; Verma, Roshan Kumar; Lal, Anupam; Mittal, Bhagwant Rai

    2016-01-01

    A 65-year-old patient, with a history of left hemi-thyroidectomy for adenomatous goiter 20 years previously, was found to have pulmonary lesions on chest X-ray, a brain lesion on computerized tomography (CT), and elevated serum thyroglobulin (Tg). While completion thyroidectomy revealed that no pathological evidence of thyroid malignancy, radioiodine-avid pulmonary, brain, and renal and bone lesions were identified on diagnostic as well as posttherapy whole body planar scintigraphy and single photon emission computed tomography-CT. Subsequent ultrasonography-guided biopsy of a renal nodule showed thyroid follicular cells. This case suggests that metastatic differentiated thyroid carcinoma should be suspected in asymptomatic patients with incidentally detected lesions, raised serum Tg, and history of thyroid lesions. PMID:26917894

  4. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) famili...

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

    2007-01-01

    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 proctocolectomy 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.

  6. Cholecystectomy and adenomatous polyps of the large bowel.

    Llamas, K J; Torlach, L G; Ward, M.; Bain, C.

    1986-01-01

    Seventy two patients (39 women) with colonic adenomas were compared with 72 adenoma free controls (39 women) to investigate the possible association between previous cholecystectomy and the subsequent development of adenomas. Data were gathered retrospectively from medical records. Overall there was no significant association between colonic adenomas and previous cholecystectomy. When women are considered separately, however, eight cases and no controls had undergone cholecystectomy (odds rat...

  7. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy.

    Bergholt, Mads Sylvest; Lin, Kan; Wang, Jianfeng; Zheng, Wei; Xu, Hongzhi; Huang, Qingwen; Ren, Jian-Lin; Ho, Khek Yu; Teh, Ming; Srivastava, Supriya; Wong, Benjamin; Yeoh, Khay Guan; Huang, Zhiwei

    2016-04-01

    Colorectal cancer can be prevented if detected early (e.g., precancerous polyps-adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber-optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real-time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1) ) and HW (i.e., 2800-3600 cm(-1) ) Raman spectra from colorectal tissue subsurface (<200 µm) for real-time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be attributed to changes in inter- and intra-cellular proteins, lipids, DNA and water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination. PMID:25850576

  8. [Future of the remaining rectum after treatment of familial polyposis (author's transl)].

    Aboulola, M; Boukheloua, B; Bouhadef, A; Illoul, G

    1978-01-01

    In the treatment of familial polyposis the conservation of the rectum is essential to assure a convenient control and rhythm of defecation. Meanwhile the future of resting polyps deserves the attention of the surgeon. Certain authors are optimistic and claim that spontaneous regression of the polyps is possible. Our experience illustrates that the rectal mucosa tends to fabricate new crops of polyps. The prolonged post operative observation of more than 4 years of polyposis in one family has permitted us to follow the evolution of the rectal mucosa and to deduce that gravity of the lesion is quite variable. The polypotique character of the rectal mucosa must influence the choice of certain surgical technic specially that nine of them achieve entire satisfaction yet. PMID:709703

  9. Hereditary mixed polyposis syndrome due to a BMPR1A mutation.

    O'Riordan, J M

    2010-06-01

    The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)-beta signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF-beta pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.

  10. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC)

    Annegret Müller; Tina Bocker Edmonston; Wolfgang Dietmaier; Reinhard Büttner; Richard Fishel; Josef Rüschoff

    2004-01-01

    Genomic instability at simple repeated sequences, termed microsatellite instability (MSI), plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC) more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the Nationa...

  11. Expression of Abelson interactor 1 (Abi1 correlates with inflammation, KRAS mutation and adenomatous change during colonic carcinogenesis.

    Konrad Steinestel

    Full Text Available BACKGROUND: Abelson interactor 1 (Abi1 is an important regulator of actin dynamics during cytoskeletal reorganization. In this study, our aim was to investigate the expression of Abi1 in colonic mucosa with and without inflammation, colonic polyps, colorectal carcinomas (CRC and metastases as well as in CRC cell lines with respect to BRAF/KRAS mutation status and to find out whether introduction of KRAS mutation or stimulation with TNFalpha enhances Abi1 protein expression in CRC cells. METHODOLOGY/PRINCIPAL FINDINGS: We immunohistochemically analyzed Abi1 protein expression in 126 tissue specimens from 95 patients and in 5 colorectal carcinoma cell lines with different mutation status by western immunoblotting. We found that Abi1 expression correlated positively with KRAS, but not BRAF mutation status in the examined tissue samples. Furthermore, Abi1 is overexpressed in inflammatory mucosa, sessile serrated polyps and adenomas, tubular adenomas, invasive CRC and CRC metastasis when compared to healthy mucosa and BRAF-mutated as well as KRAS wild-type hyperplastic polyps. Abi1 expression in carcinoma was independent of microsatellite stability of the tumor. Abi1 protein expression correlated with KRAS mutation in the analyzed CRC cell lines, and upregulation of Abi1 could be induced by TNFalpha treatment as well as transfection of wild-type CRC cells with mutant KRAS. The overexpression of Abi1 could be abolished by treatment with the PI3K-inhibitor Wortmannin after KRAS transfection. CONCLUSIONS/SIGNIFICANCE: Our results support a role for Abi1 as a downstream target of inflammatory response and adenomatous change as well as oncogenic KRAS mutation via PI3K, but not BRAF activation. Furthermore, they highlight a possible role for Abi1 as a marker for early KRAS mutation in hyperplastic polyps. Since the protein is a key player in actin dynamics, our data encourages further studies concerning the exact role of Abi1 in actin reorganization upon

  12. Additional Detection of Multiple Osteomas in a Patient with Gardner's Syndrome by Bone SPECT/CT

    Kim, Woo Hyoung; Kim, Daeweung; Kim, Chang Guhn; Kim, Myoung Hyoun [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2013-12-15

    Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which generally develops numerous polyps in the colon and rectum during the second decade of life. Gardner's syndrome is a variant of FAP which has multiple osteomas, dental abnormalities, and fibromas, with incidence ranging between 1 in 4,000 and 1 in 40,000, depending on the region. We present the case of a 35-year-old man referred to our department for bone scintigraphy who was shown to have multiple colon polyps and nuchal type fibroma. In this patient, planar image showed intensely increased uptakes of bone agent in the maxilla and mandible, which are typical findings of Gardner's syndrome. Single photon emission computed tomography/computed tomography (SPECT/CT) was acquired to accurately identify and locate abnormal uptakes detected on planar images. SPECT/CT showed numerous osteomas in the maxilla and mandible where intense uptakes of bone agent were seen. Mildly asymmetrical, focally increased uptake in the superomedial aspect of the left orbit on anterior planar image was shown to be a fontal sinus osteoma on SPECT/CT. Enhanced sensitivity of detecting lesions of SPECT/CT superior to planar scintigraphy has been reported in previous studies. In this report, additional osteomas of sphenoidal and ethmoidal sinuses, which were not seen on planar scintigraphy, were detected by SPECT/CT. This case emphasizes that nuclear physicians should be aware of the typical findings of bone scintigraphy for Gardner's syndrome and also that SPECT/CT could be helpful to diagnose additional lesions not seen on planar images.

  13. [Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)].

    Nishimoto, A; Miura, N; Oshimura, M

    1998-05-01

    To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9613131

  14. APC mutations in sporadic coloretal carcinomas from The Netherlands Cohort Study

    Lüchtenborg, M.; Weijenberg, M.P.; Roemen, G.M.J.M.; Bruïne, A.P. de; Brandt, P.A. van den; Lentjes, M.H.F.M.; Brink, M.; Engeland, M. van; Goldbohm, R.A.; Goeij, A.F.P.M. de

    2004-01-01

    The adenomatous polyposis coli (APC) gene is considered to be a gatekeeper in colorectal tumourigenesis. Inactivating mutations in APC have been reported in 34-70% of sporadic colorectal cancer patients, the majority of which occur in the mutation cluster region (MCR). In this study, tumour tissue f

  15. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development.

    Goessling, W.; North, T.E.; Lord, A.M.; Ceol, C.; Lee, S.; Weidinger, G.; Bourque, C.; Strijbosch, R.; Haramis, A.P.; Puder, M.; Clevers, H.; Moon, R.T.; Zon, L.I.

    2008-01-01

    Developmental signaling pathways hold the keys to unlocking the promise of adult tissue regeneration, and to inhibiting carcinogenesis. Patients with mutations in the Adenomatous Polyposis Coli (APC) gene are at increased risk of developing hepatoblastoma, an embryonal form of liver cancer, suggesti

  16. Thermal coagulation-induced changes of the optical properties of normal and adenomatous human colon tissues in vitro in the spectral range 400-1100 nm

    Ao Huilan; Xing Da; Wei Huajiang; Gu Huaimin [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, ina Normal University, Guangzhou 510631 (China); Wu Guoyong; Lu Jianjun [Department of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)], E-mail: xingda@scnu.edu.cn

    2008-04-21

    The absorption coefficients, the reduced scattering coefficients and the optical penetration depths for native and coagulated human normal and adenomatous colon tissues in vitro were determined over the range of 400-1100 nm using a spectrophotometer with an internal integrating sphere system, and the inverse adding-doubling method was applied to calculate the tissue optical properties from diffuse reflectance and total transmittance measurements. The experimental results showed that in the range of 400-1100 nm there were larger absorption coefficients (P < 0.01) and smaller reduced scattering coefficients (P < 0.01) for adenomatous colon tissues than for normal colon tissues, and there were smaller optical penetration depths for adenomatous colon tissues than for normal colon tissues, especially in the near-infrared wavelength. Thermal coagulation induced significant increase of the absorption coefficients and reduced scattering coefficients for the normal and adenomatous colon tissues, and significantly reduced decrease of the optical penetration depths for the normal and adenomatous colon tissues. The smaller optical penetration depth for coagulated adenomatous colon tissues is a disadvantage for laser-induced thermotherapy (LITT) and photodynamic therapy (PDT). It is necessary to adjust the application parameters of lasers to achieve optimal therapy.

  17. Gardner’s syndrome presenting as duodenal carcinoma in a young male

    Sarma YS

    2015-10-01

    Full Text Available Gardners syndrome (GS is a variant of familial adenomatous polyposis (FAP and presents with both colonic and extra colonic manifestations. It is an autosomal dominant disorder and results from mutations in adenomatous polyposis coli (APC gene. Patients with GS if not treated early will invariably develop colonic cancers at a much younger age than those with sporadic colonic carcinoma. These patients also develop other malignant tumours like duodenal cancers, gastric cancer, hepatoblastoma, papillary carcinoma of the thyroid and multifocal cholangiocarcinomas. With early diagnosis and treatment of colonic polyposis, adenocarcinoma of the duodenum has become the leading cause of death in FAP patients. The mean age at which duodenal carcinoma is diagnosed in FAP is 45-52 years. We report the rare occurrence of duodenal carcinoma as the presenting feature of Gardner’s syndrome in a young 25-year-old male with no obvious malignant changes in the colonic adenomas.

  18. N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA

    Narayan Satya

    2004-01-01

    Full Text Available Abstract Background Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG is able to induce senescence in the HCT-116 colon cancer cell line. Results Cells treated with lower concentrations of MNNG (0–25 microM for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM showed a senescence-like G0/G1 phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G2/M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G2/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and mRNA levels of APC were drastically reduced in cells treated with higher concentrations of MNNG. The loss of APC expression might lead to chromosomal instability as well as microtubular disorganization through its dissociation with tubulin. In fact, the protein level of α-tubulin was also drastically decreased in senescence-like arrested cells treated with higher concentrations of MNNG. The levels of telomeric DNA also decreased in cells treated with higher concentrations of MNNG. Conclusions These results suggest that in response to DNA alkylation damage the senescence-like arrest of HCT-116 cells was associated with decreased levels of APC protein, microtubular organization, and telomeric DNA.

  19. Neighborhood analysis of low magnification structures (glands) in healthy, adenomatous, and carcinomatous colon mucosa.

    Kayser, K; Shaver, M; Modlinger, F; Postl, K; Moyers, J J

    1986-05-01

    A new algorithm analyzing neighborhood conditions of adenomatous tissue is is introduced. Using O'Callaghan's definition of neighborhoods, a graph theory approach for measuring histomorphological structures can be created as follows: glands are defined as vertices and the coherence of neighboring glands as edges. The procedure leads to an unoriented, well-defined graph which contains information usually not measurable by conventional morphometric analysis. Measurements on healthy mucosa, tubulo-villous adenoma and highly to moderately differentiated adenocarcinoma of colon revealed statistically significant differences (p less than or equal to 0.05) for the following parameters: number of vertices, number of edges, frequency distribution of n-stars and of n-closed paths. Correct separation and reclassification of 83% of cases could be carried out using discriminant analysis. 11/15 cases (73%) could be classified correctly in a prospective group based upon the learning set. The significance of these findings for automatic pattern recognition in histopathology is discussed. PMID:3737471

  20. MALIGNANT DEGENERATION OF HAMARTOMATOUS ENTERAL POLYPOSIS – A CASE REPORT

    N. Al Hajjar

    2011-02-01

    Full Text Available Intestinal hamartomatous polyps represent a rare cause of proximal bowl obstruction and hemorrage in adults. Till 2009, there were cited less than 15 cases in the literature. Here we present the clinical observation of a patient, admitted in our clinic with the clinical diagnosis of proximal bowl obstruction, accompanied by upper digestive hemorrhage exteriorized through hematemesis, where the surgical intervention performed had showed the presence of an intestinal invagination developed upon an enteral polypod mass, along with some other enteral intraluminal polypoid masses, having different sizes, and were distributed upon a distance of 60 cm from the ligament of Treitz. A segmental eneterectomy keeping in view of the oncologicaly safety margins was performed, along with an end-to-end enetero-enteral anastomosis to restore the bowel continuity. The histopathological exam of the specimen revealed the presence of some hamartomatous polyps, along with the development of a tubular adenocarcinoma at the level of one of these polyps. Association of enteral hamartomatous polyps with enteral carcinoma and the possibility of their malignant transformation is a matter of debate in the literature, where there can be found debates supporting as well as debates negating this theory.

  1. Mantle Cell Lymphoma of Intestine Presenting as Multiple Lymphomatous Polyposis with Intussusception

    Meena N. Jadhav

    2015-01-01

    Full Text Available Mantle Cell Lymphoma (MCL is a distinct clinicopathological subtype of B-cell non-Hodgkin's lymphoma (NHL accounting for 2-10% of all NHL cases. Gastrointestinal tract (GIT is the predominant site of extranodal MCL which commonly presents as Multiple Lymphomatous Polyposis (MLP. A 60 year old male presented with pain abdomen, diarrhea and weight loss of two months duration. On colonoscopy multiple polyps were found in the entire colon and rectum. Computed tomography revealed ileo-colic intussusception with nodularity in the lead point. Histopathology suggested features of MCL. On immunohistochemistry, the tumor cells were positive for CD20, CD5, Cyclin D1, negative for CD3, CD10, CD23, and CD45 RO

  2. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Hua-Jiang Wei; Da Xing; Jian-Jun Lu; Huai-Min Gu; Guo-Yong Wu; Ying Jin

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there

  3. Regulation of Arachidonic Acid Pathway and Eosinophilic Inflammation in Chronic Rhinosinusitis/ Nasal Polyposis. Potential Role of Staphylococcus aureus Enterotoxins

    Pérez Novo, C

    2006-01-01

    linked to inflammation. Furthermore, EP2 and EP4 receptor expression was increased in chronic rhinosinusitis and nasal polyp subjects in contrast to EP1 and EP3, which were down regulated in the polyp group, suggesting a distinctive role of these receptors in the pathophysiology of nasal polyposis. Finally, based on our previous findings and parallel work of our group, we studied the influence of S. aureus enterotoxins in the regulation of both eosinophilic inflammatory and eicosanoid pathway...

  4. Investigating the Potential Role of Genetic and Epigenetic Variation of DNA Methyltransferase Genes in Hyperplastic Polyposis Syndrome

    Drini, Musa; Nicholas C. Wong; Hamish S Scott; Craig, Jeffrey M; Dobrovic, Alexander; Chelsee A Hewitt; Dow, Christofer; Young, Joanne P; Jenkins, Mark A; Saffery, Richard; Macrae, Finlay A.

    2011-01-01

    Background Hyperplastic Polyposis Syndrome (HPS) is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC). At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP), potentially linked to aberrant DNA methyltransferase (DNMT) activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT), and negative regulators of Wnt signaling (such as WIF1). In...

  5. Reprodutibilidade do estadiamento endoscópico tridimensional da polipose nasal Reproducibility of the three-dimensional endoscopic staging system for nasal polyposis

    Marcelo Castro Alves de Sousa

    2009-12-01

    Full Text Available A polipose nasossinusal é um processo inflamatório crônico da mucosa nasal, caracterizado pela presença de pólipos nasais múltiplos e bilaterais. Vários tipos de medicações têm sido usados no seu tratamento. Para estudar o resultado de diferentes formas de tratamento, é preciso alguma forma de estadiamento. OBJETIVOS: Apresentar um novo método endoscópico de estadiamento, baseado na endoscopia nasal e na avaliação tridimensional dos pólipos, comparar sua reprodutibilidade entre outros dois métodos já difundidos. FORMA DE ESTUDO: Estudo de coorte histórica com corte transversal. MATERIAL E MÉTODO: Três examinadores avaliaram exames de 20 pacientes portadores de polipose nasossinusal em diferentes momentos, antes e 15 e 30 dias após o início de um tratamento com prednisona, na dose de 1 mg/kg/dia por 7 dias. Foi avaliado o grau de concordância entre os examinadores para cada método, utilizando-se o Kappa múltiplo para análise estatística. RESULTADOS: Os três métodos mostraram-se reprodutíveis, sendo que o método proposto apresentou menor concordância entre os examinadores. CONCLUSÃO: O estadiamento proposto mostrou-se reprodutível, apesar de apresentar menor concordância do que os outros dois estadiamentos.Nasal Polyposis is a chronic inflammatory process of the nasal mucosa, characterized by multiple and bilateral nasal polyps. Different drugs have been used in its treatment. In order to study the results of different treatment modalities it is necessary to have some kind of staging. AIM: to present a new endoscopic staging method, based on nasal endoscopy and on the three-dimensional nasal polyp assessment; and compare its reproducibility with that from two other systems already established in the literature. STUDY DESIGN: Cohort study. MATERIAL AND METHODS: Three experts assessed the exams of 20 patients with nasal polyposis at different times, before, at 15 and at 30 days after the start of oral prednisone

  6. Investigating the potential role of genetic and epigenetic variation of DNA methyltransferase genes in hyperplastic polyposis syndrome.

    Musa Drini

    Full Text Available BACKGROUND: Hyperplastic Polyposis Syndrome (HPS is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC. At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP, potentially linked to aberrant DNA methyltransferase (DNMT activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT, and negative regulators of Wnt signaling (such as WIF1. In this study, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, in the aetiology of HPS. METHODS: We utilized high resolution melting (HRM analysis to screen 45 cases with HPS for novel sequence variants in DNMT1, DNMT3A, DNMT3B, and DNMT3L. 21 polyps from 13 patients were screened for BRAF and KRAS mutations, with assessment of promoter methylation in the DNMT1, DNMT3A, DNMT3B, DNMT3L MLH1, MGMT, and WIF1 gene promoters. RESULTS: No pathologic germline mutations were observed in any DNA-methyltransferase gene. However, the T allele of rs62106244 (intron 10 of DNMT1 gene was over-represented in cases with HPS (p<0.01 compared with population controls. The DNMT1, DNMT3A and DNMT3B promoters were unmethylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells with methylation level negatively correlated to expression level in normal colonic tissue. DNMT3L promoter hypomethylation was more often found in polyps harbouring KRAS mutations (p = 0.0053. BRAF mutations were common (11 out of 21 polyps, whilst KRAS mutations were identified in 4 of 21 polyps. CONCLUSIONS: Genetic or epigenetic alterations in DNMT genes do not appear to be associated with HPS, but further investigation of genetic variation at rs62106244 is justified given the high frequency of the minor allele in this case series.

  7. Genetic testing for young-onset colorectal cancer: case report and evidence-based clinical guidelines

    Zhou, Yaolin; Boardman, Lisa A; Miller, Robert C.

    2010-01-01

    Background Young-onset colorectal cancer is clinicopathologically different from older-onset colorectal cancer and tends to occur in patients with hereditary germline conditions such as Lynch syndrome and familial adenomatous polyposis. Case report. We describe the case of a 44-year-old man with a paternal history of colon polyps, a personal 2-year history of hematochezia, and a diagnosis of rectal cancer. Further clinical evaluation of the patient at our institution determined the cancer to ...

  8. Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

    Gallinger Steven; Chetty Runjan; Goncalves Jason; Salahshor Sima; Woodgett James R

    2005-01-01

    Abstract Background APC (Adenomatous polyposis coli) plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process. Methods To elucidate the biological dysregulation underlying adenoma formation we examined global gene express...

  9. Hereditary Colorectal Cancer: Registration, Screening and Prognostic Biomarker Analysis

    Barrow, Paul

    2015-01-01

    Aims: The purpose of the research was to investigate the benefits of a hereditary colorectal cancer registry in the management of patients and families with Lynch syndrome. In study one, a systematic review was performed to quantify the impact of registration and screening on colorectal cancer (CRC) incidence and mortality, with comparison between familial adenomatous polyposis (FAP) and Lynch syndrome (LS). In study two, a regional Lynch syndrome registry was utilised to evaluate the uptake ...

  10. The insulin receptor substrate 1 (irs1) in intestinal epithelial differentiation and in colorectal cancer.

    Esposito, DL; Aru, F; Lattanzio, R; Morgano, A.; Abbondanza, M; Malekzadeh, R; BISHEHSARI F; Valanzano, R; Russo, A; Piantelli, M; Moschetta, A; Lotti, LV; MARIANI-COSTANTINI R

    2012-01-01

    Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and ...

  11. Colon Cancer Metastatic to the Biliary Tree.

    Strauss, Alexandra T; Clayton, Steven B; Markow, Michael; Mamel, Jay

    2016-04-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD. PMID:27144209

  12. Genetic association- and linkage studies in colorectal cancer

    Holst, Susanna von

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) ha...

  13. Retroperitoneal fibromatosis presenting as a presacral mass

    Aggressive fibromatosis arising from the retroperitoneum is extremely rare. It may occur in association with previous trauma, abdominal surgery, drugs, Gardner’s syndrome, or familial adenomatous polyposis. We report a case of retroperitoneal fibromatosis presenting as a presacral mass with an infiltrating nature, relatively intense enhancement on enhanced computed tomography scanning, and low-signal intensity on T2-weighted magnetic resonance imaging in a patient with no significant medical or surgical history

  14. Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities.

    Silva, Patrícia; Albuquerque, Cristina; Lage, Pedro; Fontes, Vanessa; Fonseca, Ricardo; Vitoriano, Inês; Filipe, Bruno; Rodrigues, Paula; Moita, Susana; Ferreira, Sara; Sousa, Rita; Claro, Isabel; Nobre Leitão, Carlos; Chaves, Paula; Dias Pereira, António

    2016-09-01

    Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0x10-7), in most early lesions. Proximal/whole‑colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatellite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2x10-4; 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress. PMID:27430658

  15. JP-HHT phenotype in Danish patients with SMAD4 mutations

    Jelsig, A M; Tørring, P M; Kjeldsen, A D;

    2016-01-01

    Patients with germline mutations in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT): the JP-HHT syndrome. The complete phenotypic picture of this syndrome is only just emerging. We describe the clinical characteristics of 14...

  16. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  17. Percutaneous ethanol injection therapy of adenomatous hyperplastic nodules in cirrhotic liver disease

    In this study, we treated a total of 23 AHNs in 15 patients with percutaneous ethanol injection (PEI). The treatment included 6 to 8 PEIs, performed on an out-patient basis under sonographic guidance. A 22 G (0.7 mm) spinal needle was used. The total amount of alcohol delivered into each lesion was 8 to 25 ml (mean 14.9 ml). At the end of treatment, complete necrosis of the nodule was proved in all cases by multiple fine-needle biopsies and confirmed by CT and MR findings. During follow-up (9-41 months, mean 24 months) no recurrences were demonstrated. However, HCC occurred elsewhere in the liver of 4 patients and additional AHNs were detected in 2 patients. Thus, PEI proved able to cause complete ablation of AHNs, presumably preventing their malignant transformation. (orig.)

  18. Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells

    A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [3H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance

  19. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen;

    1997-01-01

    were compared with 870 patients with sporadic colorectal cancer. RESULTS: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchromous tumours (7% versus 1%), more...

  20. A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

    Mai Phuong L

    2007-03-01

    Full Text Available Abstract Background Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. Case presentation The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene, Carney complex (PRKAR1A gene, and multiple endocrine neoplasia syndrome type 1 (MEN1 gene; no deleterious mutations were identified. Discussion The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further.

  1. Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment

    Suzie Hyeona Kang

    2015-02-01

    Full Text Available Although cystic fibrosis (CF is an irreversible genetic disease, advances in treatment have increased the life expectancy of CF patients. Upper airway involvement, which is mainly due to pathological changes in the paranasal sinuses, is prevalent in CF patients, although many are only mildly symptomatic (with few symptoms. The objective of this literature review was to discuss the pathophysiology and current therapeutic management of chronic rhinosinusitis (CRS in CF patients. The review was based on current evidence, which was classified in accordance with the Oxford Centre for Evidence-Based Medicine criteria. When symptomatic, CRS with nasal polyps can affect quality of life and can lead to pulmonary exacerbations, given that the paranasal sinuses can be colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection with P. aeruginosa plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Although clinical treatment of the upper airways is recommended as initial management, this recommendation is often extrapolated from studies of CRS in the general population. When sinonasal disease is refractory to noninvasive therapy, surgery is indicated. Further studies are needed in order to gain a better understanding of upper airway involvement and improve the management of CRS in CF patients, with the objective of preserving lung function and avoiding unnecessary invasive procedures.

  2. A novel predictive marker for the recurrence of nasal polyposis following endoscopic sinus surgery.

    Boztepe, Osman Fatih; Gün, Taylan; Demir, Meltem; Gür, Özer Erdem; Ozel, Deniz; Doğru, Harun

    2016-06-01

    We aimed to determine the value of neutrophil-to-lymphocyte (NLR) ratio for prediction of recurrence in patients subjected to endoscopic sinus surgery. Higher neutrophil counts mean more chronic inflammation so the NLR value could show the inflammatory level resulting with higher incidence of recurrence. From January 2011 to March 2013, we performed a retrospective review of the complete blood count samples from 192 patients with chronic sinusitis who underwent endoscopic sinus surgery. The patients were divided into two groups based on the presence of nasal polyps. NLR and platelet-to-lymphocyte (PLR) ratios were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value for significant differences in variables between the recurrence and non-recurrence groups. The ROC analysis results revealed an NLR cut-off of 3.13 and a PLR cut-off of 208.75. Our analysis revealed that NLR is an independent risk factor for recurrence of chronic sinusitis in patients subjected to endoscopic sinus surgery (p = 0.006), whereas the PLR was not a predictive factor for recurrence (p = 0.167). Our study revealed that the NLR could be used to predict disease recurrence before endoscopic sinus surgery. However, additional studies are needed to confirm these results. PMID:26285781

  3. Herpes viruses and human papilloma virus in nasal polyposis and controls

    Dimitrios Ioannidis

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

  4. Mismatch repair mRNA and protein expression in intestinal adenocarcinoma in sika deer (Cervus nippon) resembling heritable non-polyposis colorectal cancer in man.

    Jahns, H; Browne, J A

    2015-01-01

    Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer. PMID:25678423

  5. Complicações imediatas e tardias após cirurgia de reservatório ileal na polipose adenomatosa familiar Short-term and long-term postoperative complications after ileal pouch-anal anastomosis in familial adenomatous polyposis

    Raquel Franco Leal; Maria de Lourdes Setsuko Ayrisono; Cláudio Saddy Rodrigues Coy; João José Fagundes; Juvenal Ricardo Navarro Góes

    2008-01-01

    RACIONAL: A retocolectomia total com confecção de reservatório ileal é cirurgia ideal para o tratamento do cólon e reto dos doentes com polipose adenomatosa familiar, no entanto pode estar associada a complicações no pós-operatório imediato e tardio. OBJETIVO: Estudar as complicações pós-operatórias da cirurgia do reservatório ileal na polipose adenomatosa familiar. MÉTODOS: Estudo retrospectivo de 69 doentes com polipose adenomatosa familiar submetidos a cirurgia de reservatório ileal no per...

  6. Clinical Inquiry. Does turmeric relieve inflammatory conditions?

    White, Brett; Judkins, Dolores Zegar

    2011-03-01

    Yes, but data aren't plentiful. Limited evidence suggests that turmeric and its active compound, curcumin, are effective for rheumatoid arthritis and other inflammatory conditions (strength of recommendation [SOR]: C, primarily low-quality cohort studies with small patient numbers). Curcumin has shown limited benefit for patients with psoriasis, inflammatory bowel disease (IBS), inflammatory eye diseases, familial adenomatous polyposis, and kidney transplantation (SOR: B, small, short randomized controlled trials [RCTs]). No evidence indicates that curcumin helps patients with human immunodeficiency virus (HIV) (SOR: B, single RCT). PMID:21369559

  7. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need. PMID:26475526

  8. Influence of Chronic Moderate Sleep Restriction and Exercise on Inflammation and Carcinogenesis in Mice

    Zielinski, Mark R.; Davis, J. Mark; Fadel, James R.; YOUNGSTEDT, SHAWN D.

    2012-01-01

    The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min+/-) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1 h/day) vs. sedentary control. Wild-type control mice underwent identical experime...

  9. A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia

    Rivera, B.; J. Perea; Sánchez, E.; Villapún, M; Sánchez-Tomé, E; Mercadillo, F; Robledo, M; Benítez, J; Urioste, M.

    2013-01-01

    Truncating mutations in the AXIN2 gene, a key regulator of β-catenin degradation in the Wnt pathway, have been reported in three families with gastrointestinal adenomatous polyposis and features of ectodermal dysplasia. However, the role of AXIN2 in familial adenomatous polyposis (FAP) syndrome is not completely understood. We performed an in-depth study of APC and MUTYH, and ruled out their implication in 23 FAP families. We then investigated the role of other genes involved in the Wnt pathw...

  10. Targeting Stem Cell Behavior in Desmoid Tumors (Aggressive Fibromatosis) by Inhibiting Hedgehog Signaling1

    Ghanbari-Azarnier, Ronak; Sato, Shingo; Wei, Qingxia; Al-Jazrawe, Mushriq; Alman, Benjamin A.

    2013-01-01

    Desmoid tumor (also called aggressive fibromatosis) is a lesion of mesenchymal origin that can occur as a sporadic tumor or a manifestation of the preneoplastic syndrome, familial adenomatous polyposis caused by a mutation in adenomatous polyposis coli (APC). This tumor type is characterized by the stabilization of β-catenin and activation of Tcf-mediated transcription. Cell transplantation data suggest that desmoid tumors are derived from mesenchymal progenitor cells (MSCs). As such, modulat...

  11. Successful outcome after laparoscopic surgery for sporadic colonic desmoid tumor with β-catenin mutation: a case report

    Gunji, Shutaro; Kawada, Kenji; Kawada, Mayumi; Hasegawa, Suguru; Sakai, Yoshiharu

    2013-01-01

    Introduction Desmoid tumors (also called aggressive fibromatosis) are histologically benign, but have a strong tendency to recur locally after resection. They are rare neoplastic tumors that may occur sporadically or in association with familial adenomatous polyposis caused by a germline mutation in the adenomatous polyposis coli gene. The etiology of desmoid tumors is unknown, but their association with a history of abdominal surgery, trauma, and estrogen therapy is well known. Case presenta...

  12. Juvenil polypose-syndrom og hereditær hæmoragisk telangiektasi hos en patient med SMAD4-mutation

    Jelsig, Anne Marie; Tørring, Pernille Mathiesen; Wikman, Friedrik;

    2014-01-01

    Germ line mutations in SMAD4 can cause both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia syndrome. In this case we present a 37-year-old man with a frameshift mutation in SMAD4. The patient had multiple polyps in the gastrointestinal tract and was diagnosed with colon...... cancer at the age of 21 and gastro-oesophageal junction cancer at the age of 37. Furthermore the patient had telangiectasias and recurrent epistaxis....

  13. Juvenile Polyposis Syndrome

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... is assumed if a person’s symptoms and family history fits 1 of the 3 categories listed above. ...

  14. Hereditary Mixed Polyposis Syndrome

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... is suspected in individuals and families with a history of multiple colon polyps of different types. It ...

  15. Effect of differently sized nanoparticles’ accumulation on the optical properties of ex vivo normal and adenomatous human colon tissue with OCT imaging and diffuse reflectance spectra

    Using optical coherence tomography (OCT) and diffuse reflectance spectra, we investigated the dynamics of titanium dioxide (TiO2) nanoparticles, of different sizes, when penetrating and accumulating in human normal colon tissue (NC) and adenomatous colon tissue (AC). The process of nanoparticle penetration and accumulation in biotissue is accompanied by changes in the optical properties of tissue. Continuous OCT monitoring showed that, after application of TiO2 nanoparticles, the OCT signal intensities of NC and ac both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The average attenuation coefficient decreased from 4.03 ± 0.36 to 2.68 ± 0.24 mm−1 at approximately 127 min for NC with 60 nm TiO2, from 4.14 ± 0.38 to 2.91 ± 0.27 mm−1 at about 148 min for NC with 100 nm TiO2, from 8.49 ± 0.77 to 3.54 ± 0.34 mm−1 at about 110 min for AC with 60 nm TiO2, and from 8.61 ± 0.79 to 3.89 ± 0.41 mm−1 at about 128 min for AC with 100 nm TiO2, respectively. Spectral measurements confirm that the nanoparticles penetrate and accumulate in NC and AC. The results suggest that the penetration and accumulation of TiO2 nanoparticles have significant effects on the optical properties of NC and AC. (letter)

  16. A Case of Adenomatous Goiter Involving Diffuse, Acute, and Painful Thyroid Enlargement after Fine-Needle Aspiration Cytology

    Toshiro Shimo

    2014-01-01

    Full Text Available The patient was a 44-year-old woman who exhibited a diffuse goiter during health screening. Her medical history did not include any significant medication-based treatment. An echographic examination detected a solid cystic tumor, which measured 21 × 14 × 10 mm, in her right thyroid lobe; however, she displayed normal thyroid function. After fine-needle aspiration cytology had been performed with a 22 G injection needle, the patient immediately complained of compression and pain extending from the front of her neck to her lower chin, which was not accompanied by dyspnea. A second echographic examination revealed diffuse and edematous enlargement and increased internal blood flow in the bilateral thyroid lobes as well as a thyroid nodule. We immediately iced the patient’s neck and administered 125 mg methylprednisolone via an intravenous infusion. Within one hour, her symptoms had markedly improved, but acute pain remained. Thus, we continued the steroid (prednisone treatment, but the dose was gradually reduced from 10 mg/day to 5 mg/day at 1 week after the patient’s symptoms disappeared. The mechanism responsible for the patient’s condition remains unclear.

  17. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Research highlights: → Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. → Expression profiling of apoptosis-related genes in ApcMin/+ mice revealed the differential expression of pro-apoptotic Bok and Bax. → APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. → Blocking of β-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the ApcMin/+ mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem

  18. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    Papp, Janos; Kovacs, Marietta E; Olah, Edith

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population. PMID:17569143

  19. Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing

    Janos Papp; Marietta E Kovacs; Edith Olah

    2007-01-01

    AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families.METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA).RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remAlning two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.

  20. Endogenous conversion of ω-6 to ω-3 polyunsaturated fatty acids in fat-1 mice attenuated intestinal polyposis by either inhibiting COX-2/β-catenin signaling or activating 15-PGDH/IL-18.

    Han, Young-Min; Park, Jong-Min; Cha, Ji-Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-05-01

    Omega-3 polyunsaturated fatty acids (ω-3PUFAs) have inhibitory effects in various preclinical cancer models, but their effects in intestinal polyposis have never been examined. As attempts have been made to use nutritional intervention to counteract colon cancer development, in this study we evaluated the effects of ω-3 PUFAs on intestinal polyposis in the Apc(Min/) (+) mouse model. The experimental groups included wild-type C56BL/6 mice, Apc(Min/) (+) mice, fat-1 transgenic mice expressing an n-3 desaturase to enable ω-3 PUFA synthesis, and Apc(Min/) (+) × fat-1 double-transgenic mice; all mice were 20 weeks of age. Small intestines were collected for gross and pathologic evaluation, including assessment of polyp number and size, followed by immunohistochemical staining and Western blotting. After administration of various concentrations of ω-3 PUFAs, PUFA levels were measured in small intestine tissue by GC/MS/MS analysis to compare with PUFA synthesis of between C57BL6 and fat-1mice. As a result, ω-3 PUFAs significantly attenuated Apc mutation-induced intestinal polyposis accompanied with significant inhibition of Wnt/β-catenin signaling, COX-2 and PGE2, but induced significant levels of 15-PGDH. In addition, significant induction of the inflammasome-related substrates as IL-1β and IL-18 and activation of caspase-1 was observed in Apc(Min/) (+) × fat-1 mice. Administration of at least 3 g/60 kg ω-3 PUFAs was equivalent to ω-3 PUFAs produced in fat-1 mice and resulted in significant increase in the expression of IL-1β, caspase-3 and IL-18, as seen in Apc(Min/) (+) × fat-1 mice. We conclude that ω-3PUFAs can prevent intestinal polyp formation by inhibition of Wnt/β-catenin signaling, but increased levels of 15-PGDH and IL-18. PMID:26650508

  1. An individual with both MUTYH-associated polyposis and Lynch syndrome identified by multi-gene hereditary cancer panel testing: a case report

    Stephanie A Cohen

    2016-03-01

    Full Text Available The utilization of next-generation sequencing technology to interrogate multiple genes simultaneously is being utilized more frequently in hereditary cancer testing. While this has benefits of reducing cost and allowing clinicians to cast a wide net in the elucidation of their patient’s cancer, panel testing has the potential to reveal unexpected information. We report on a proband with pathogenic variants resulting in two different hereditary colon cancer syndromes.A 39-year-old male with a history of colon cancer, more than 20 colon polyps and a family history of colon cancer presented for genetic counseling. Testing with a 7-gene high-risk hereditary colon cancer panel identified a homozygous pathogenic variant, c.1187G>A (p.Gly396Asp in MUTYH, and a likely pathogenic duplication of exon 7 in MSH2. Since this test result, the proband’s mother was diagnosed with colon cancer; subsequent genetic testing confirmed she also carries the likely pathogenic duplication in the MSH2 gene.Although the cancer risk in individuals who carry multiple pathogenic variants has not been established for combined biallelic MUTYH-associated polyposis and Lynch syndrome, the identification of multiple pathogenic variants does allow for screening for cancers associated with both syndromes and has implications for cancer risk for family members. In particular, this has significant impact on those who test negative for a known familial pathogenic variant, yet could be still be at risk for cancer due to a second pathogenic variant in a family. More information is needed on the frequency of occurrence of multiple pathogenic variants, as well as the phenotypic spectrum when multiple pathogenic variants are present.

  2. Avaliação da concordância interobservadores na análise da polipose nasossinusal por meio da tomografia computadorizada Evaluation of the concordance between observers in sinunasal polyposis through computed tomographic analysis

    Elaine A. Mendes

    2004-08-01

    Full Text Available Polipose nasossinusal (PNS é uma entidade de etiologia controversa, caracterizada por uma condição inflamatória da superfície mucosa das fossas nasais e seios paranasais, bilateralmente. A queixa principal do paciente consiste na obstrução nasal e, ao exame físico, observam-se freqüentemente massas polipóides ocupando as cavidades nasais em extensões variáveis. Além da rinoscopia anterior e da endoscopia nasal, o uso da tomografia computadorizada (TC torna-se necessário para avaliação das fossas nasais e da presença ou não do acometimento dos seios paranasais por essas massas, bem como a sua extensão. Este trabalho tem como objetivo avaliar a concordância interobservadores, por meio da análise da tomografia computadorizada, de 32 casos de PNS. FORMA DE ESTUDO: Clínico prospectivo. CASUÍSTICA E MÉTODOS: Foram avaliadas 32 TC de pacientes portadores PNS por dois observadores experientes, separadamente, em relação à presença ou não de 3 sinais tomográficos sugestivos dessa doença: (1 alargamento infundibular do complexo ostiomeatal, (2 abaulamento lateral da lâmina papirácea e (3 apagamento do trabeculado ósseo etmoidal. RESULTADOS: Observou-se Qui-quadrado não significante para o primeiro e segundo sinais (p=0,7055 e p=0,2057 e significante para o terceiro (p=0,0040. Contudo, o coeficiente de correlação de Kendall entre os dois observadores foi significante para os três sinais tomográficos acima citados (pSinonasal polyposis (SNP is a condition with a controversial aethiology, known by bilaterally inflammatory mucous membranes of nasal and paranasal sinuses. The major patient's complaint is nasal obstruction, and polypoid masses in different sizes can be found during nasal cavity examination. Beyond anterior rhinoscophy and nasal endoscopy, screening sinus computed tomography (SSCT is necessary to measure the size and the extent of the polyps into nasal cavities and paranasal sinuses. The purpose of this

  3. Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

    Dourisboure Ricardo J

    2006-01-01

    Full Text Available Abstract Background Hereditary non-polyposis colon cancer (HNPCC is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. Methods Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250. Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. Results Three of five microsatellite markers (BAT-25, BAT-26 and D5S346 presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H. We identified in the HNPCC family a novel germline missense (c.1864C>A mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr amino acid substitution. Conclusion This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT Database this is the first report of this mutation.

  4. An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours

    Abdalla, Sala; Wilkinson, Michelle; Wilsher, Mark; Uzkalnis, Aleksandras

    2016-01-01

    Introduction Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize. There is frequent association with females of reproductive age, a history of abdominal surgery or trauma and a family history of fibromatoses. Intra-abdominal DTs are infrequently sporadic and more commonly associated with inherited disorders such as familial adenomatous polyposis (FAP), attenuated FAP and Gardener’s syndrome. Presentation of case The authors report a rare case of small bowel obstruction and perforation secondary to sporadic, synchronous intra-abdominal DTs in a 54-year old man with atypical symptoms and no risk factors or family history. Discussion Intra-abdominal DTs have a worse prognosis as they can cause intestinal bleeding, obstruction and perforation. Due to the rarity of these tumours there are no clear guidelines on their management and this is instead based on small case series from specialist centres. In the non-acute setting patients with sporadic intra-abdominal DTs should be managed in a specialist sarcoma unit by a multidisciplinary team. In the presence of FAP or other polyposis syndromes patients with DTs should be managed at a specialist colorectal unit. Emergent presentations require emergency surgery in suitable candidates. Conclusion In non-emergency presentations of DTs, it is essential to exclude FAP, AFAP and other hereditary polyposis syndromes since this affects treatment and subsequent follow-up. PMID:26866881

  5. Different activations of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis.

    Hirschberg, Andor; Kiss, Maria; Kadocsa, Edit; Polyanka, Hilda; Szabo, Kornelia; Razga, Zsolt; Bella, Zsolt; Tiszlavicz, Laszlo; Kemeny, Lajos

    2016-07-01

    Both up- and down-regulation of the Toll-like receptors (TLRs) and antimicrobial peptides (AMPs) of the sinonasal mucosa have already been associated with the pathogenesis of chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps. The objective of this study was to determine the expression of all known TLR and several AMP genes and some selected proteins in association with allergy, asthma and aspirin intolerance (ASA) in CRS subgroups. RT-PCR was applied to measure the mRNA expressions of 10 TLRs, four defensins, lysozyme, cathelicidin and lactoferrin (LTF) in sinonasal samples from patients with CRSsNP (n = 19), CRSwNP [ASA(-): 17; ASA(+): 7] and in control subjects (n = 12). Protein expressions were detected with immunohistochemistry (n = 10). Statistical analysis was done with the Kruskal-Wallis ANOVA, Mann-Whitney U, and Student t test. TLR2, TLR5, TLR6, TLR7, TLR8, TLR9, β-defensins 1 and 4, cathelicidin and LTF mRNA expressions were significantly (p < 0.05) increased in CRSwNP, whereas only TLR2 and LTF were up-regulated in CRSsNP compared to controls. There was no statistical difference in respect of allergy, aspirin intolerance and smoking between CRSsNP, ASA(-) and ASA(+) CRSwNP patients. TLR2, TLR3, TLR4, LTF, β defensin 2 and lysozyme protein expressions were found to be elevated in macrophages of CRSwNP samples (p < 0.05). Gene expression analysis showed markedly different expressions in CRSwNP (6 out of 10 TLR and 4 out of 7 AMP genes were up-regulated) compared to CRSsNP (1/10, 1/7). The distinct activation of the innate immunity may support the concept that CRSsNP and CRSwNP are different subtypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application. PMID:26518209

  6. Mutational Hotspots in the Mitochondrial D-Loop Region of Cancerous and Precancerous Colorectal Lesions in Egyptian Patients

    Kassem, Abdel Meguid; El-Guendy, Nadia; Tantawy, Marwa; Abdelhady, Hala; El-Ghor, Akmal; Abdel Wahab, Abdel Hady

    2011-01-01

    Mutations in the mitochondrial genome (mtDNA) are associated with different types of cancer, specifically colorectal cancer (CRC). However, few studies have been performed on precancerous lesions, such as ulcerative colitis (UC) lesions and adenomatous polyps (AP). The aim of this study was to identify mtDNA mutations in the cancerous and precancerous lesions of Egyptian patients. An analysis of the mutations found in six regions of the mtDNA genome (ND1, ND5, COI, tRNAser, D-loop 1, and 2) i...

  7. Study on the origin and nature of the adenomatoid odontogenic tumor by immunohistochemistry Estudo da origem e natureza do tumor odontogênico adenomatóide pela imunoistoquímica

    Marcelo Macedo Crivelini

    2005-12-01

    Full Text Available The adenomatoid odontogenic tumor (AOT is a clinically benign lesion. Discussions about the AOT hamartomatous or neoplastic nature, and the probable odontogenic epithelial cell it originates from still exist. This research aimed to study and discuss the subject by the immunohistochemical detection of cytokeratins, laminin, collagen IV, PCNA and p53 in 8 tumor samples and 8 dental follicle samples containing reduced enamel epithelium. The results have shown that CK14 labelling indicated differentiation grades for secreting ameloblasts or ameloblasts in the post-secreting stage in the adenomatoid structure of AOT. Laminin, found on the luminal surface of adenomatoid structures, was compatible with the reduced enamel epithelium during the "protective stage of amelogenesis". PCNA specifically labelled the spindled areas and peripheral cords of the AOT, indicating that these areas are responsible for tumor growth. After considerations about pathogenesis, the authors suggested that the nature of AOT is hamartomatous with histogenesis from the reduced enamel epithelium.O tumor odontogênico adenomatóide (TOA é uma lesão clinicamente benigna, cujas discussões acerca de sua natureza hamartomatosa ou neoplásica, e provável célula epitelial odontogênica de origem ainda existem. Este projeto de pesquisa teve por objetivo estudar o assunto através da detecção imuno-histoquímica das citoqueratinas, laminina, colágeno IV, PCNA e p53, utilizando-se para isso 08 amostras do tumor e 08 amostras de folículo pericoronário contendo epitélio reduzido do órgão do esmalte (EROE. Os resultados mostraram que a marcação da CK14 sinalizou graus de diferenciação para ameloblastos secretores ou pós-secretores nas estruturas adenomatóides do TOA, e a laminina presente em sua superfície luminal foi compatível com o EROE durante o "estágio protetor" da amelogênese. O PCNA marcou especificamente áreas enoveladas e cordões periféricos do TOA

  8. Cutaneous manifestations of gastrointestinal disease: part I.

    Shah, Kejal R; Boland, C Richard; Patel, Mahir; Thrash, Breck; Menter, Alan

    2013-02-01

    Cutaneous findings are not uncommonly a concomitant finding in patients afflicted with gastrointestinal (GI) diseases. The dermatologic manifestations may precede clinically evident GI disease. Part I of this 2-part CME review focuses on dermatologic findings as they relate to hereditary and nonhereditary polyposis disorders and paraneoplastic disorders. A number of hereditary GI disorders have an increased risk of colorectal carcinomas. These disorders include familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Each disease has its own cutaneous signature that aids dermatologists in the early diagnosis and detection of hereditary GI malignancy. These disease processes are associated with particular gene mutations that can be used in screening and to guide additional genetic counseling. In addition, there is a group of hamartomatous syndromes, some of which are associated with phosphatase and tensin homolog (PTEN) gene mutations, which present with concurrent skin findings. These include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, and Cronkhite-Canada syndrome. Finally, paraneoplastic disorders are another subcategory of GI diseases associated with cutaneous manifestations, including malignant acanthosis nigricans, Leser-Trélat sign, tylosis, Plummer-Vinson syndrome, necrolytic migratory erythema, perianal extramammary Paget disease, carcinoid syndrome, paraneoplastic dermatomyositis, and paraneoplastic pemphigus. Each of these disease processes have been shown to be associated with an increased risk of GI malignancy. This underscores the important role of dermatologists in the diagnosis, detection, monitoring, and treatment of these disorders while consulting and interacting with their GI colleagues. PMID:23317980

  9. TTF-1-positive oncocytic sellar tumor with follicle formation/ependymal differentiation: non-adenomatous tumor capable of two different interpretations as a pituicytoma or a spindle cell oncocytoma.

    Yoshimoto, Toyoki; Takahashi-Fujigasaki, Junko; Inoshita, Naoko; Fukuhara, Noriaki; Nishioka, Hiroshi; Yamada, Shozo

    2015-07-01

    We describe herein the unique case of a 70-year-old male with a TTF-1-positive non-adenomatous sellar tumor that has unusual morphological and immunohistochemical features. MRI examination detected a 2-cm sellar mass that was enhanced heterogeneously. By histology, the tumor was composed of epithelioid and oncocytic cells arranged in a trabecular pattern with occasional luminal structures. The lesion was diffusely immunopositive for thyroid transcription factor-1 (TTF-1) and vimentin but negative for S100 protein and GFAP. Immunoreactivity for epithelial membrane antigen, low molecular weight cytokeratin (CAM 5.2), and neuronal markers was also observed in the tumor cells. By electron microscopy, the tumor cells were filled with abundant mitochondria and extended microvillous projections into small extracellular and intracellular lumens. TTF-1 is considered to be an excellent marker of pituicytes, specialized glia of the neurohypophysis. This case can be regarded as a variant of pituicytoma, showing both ependymal differentiation and oncocytic changes. However, the immunoprofile was not completely consistent with a pituicyte lineage; the epithelial features suggested a possibility of folliculostellate cell origin. TTF-1-positive sellar neoplasms might therefore have variable morphological and immunohistochemical profiles. For suitable classification of TTF-1 positive sellar neoplasms, their histological features should be carefully re-evaluated. PMID:25893822

  10. Radiation-induced intestinal neoplasia in a genetically-predisposed mouse (Min)

    A mouse lineage with inherited predisposition to multiple intestinal neoplasia (min) has been proposed as a model to study human colorectal cancer. Min mice are heterozygous for the adenomatous polyposis coli (Apc) gene implicated in human familial adenomatous polyposis (FAP). There is an increased risk of intestinal cancer in humans following radiation exposure and the min mouse model may be used to further our understanding of the molecular mechanisms involved. The present study showed a 2 Gy dose of x-rays doubles the tumour numbers in the murine gastrointestinal tract of F1 min heterozygotes. The distribution of tumours through the gut was also recorded. (authors)

  11. Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)*

    Tanneberger, Kristina; Pfister, Astrid S.; Kriz, Vitezslav; Bryja, Vitezslav; Schambony, Alexandra; Behrens, Jürgen

    2011-01-01

    Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing β-catenin degradation. We show here that Amer1 directly interacts with the armadillo repeats of β-catenin via a domain consisting of repeated arginine-glutamic acid-alanine (REA) motifs, and that Amer1 assembles the β-catenin destruction complex at the plasma membrane by recruiting β-catenin, adenomatous polyposis coli, and Axin/Conductin. Deletion or specific mutations of ...

  12. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  13. Stratification of the risk for nuclear medicine in illness coronary stable

    Papillary carcinoma of the thyroid (PTC) is the most prevalent malignancy of the thyroid gland. Although the majority of lesions are sporadic tumors, an established relationship exists between familial adenomatous polyposis and PTC. Moreover, some authors postulate the existence of familial PTC as a distinct entity. Evidence for this is limited, however, they're being few well-characterized descriptions of pedigrees with high prevalence of PTC. In this article three cases of papillary carcinoma of the thyroid are presented who belong to the same family, all of them of the feminine gender, and not affected by the familial adenomatous polyposis syndrome. Some considerations are made about the etiology, diagnosis and prognosis

  14. Promoter SNPs rs116896264 and rs73933062 form a distinct haplotype and are associated with galectin-4 overexpression in colorectal cancer.

    Helwa, Reham; Ramadan, Mohamed; Abdel-Wahab, Abdel-Hady A; Knappskog, Stian; Bauer, Andrea S

    2016-07-01

    Galectin-4 is a member of the galectin family which consists of 15 galactoside-binding proteins. Previously, galectin-4 has been shown to have a role in cancer progression and metastasis and it is found upregulated in many solid tumours, including colorectal cancer (CRC). Recently, the role in the metastatic process was suggested to be via promoting cancer cells to adhere to blood vascular endothelium. In the present study, the regulatory region of LGALS4 (galectin-4) in seven colon cell lines was investigated with respect to genetic variation that could be linked to expression levels and therefore a tumourigenic effect. Interestingly, qRT-PCR and sequencing results revealed that galectin-4 upregulation is associated with SNPs rs116896264 and rs73933062. By use of luciferase reporter- and pull-down assays, we confirmed the association between the gene upregulation and the two SNPs. Also, using pull-down assay followed by mass spectrometry, we found that the presence rs116896264 and rs73933062 is changing transcription factors binding sites. In order to assess the frequencies of the two SNPs among colon cancer patients and healthy individuals, we genotyped 75 colon cancer patients, 12 patients with adenomatous polyposis and 17 patients with ulcerative colitis and we performed data mining in the 1000 genomes databank. We found the two SNPs co-occuring in 21% of 75 CRC patients, 0 out of 12 patients of adenomatous polyposis, and 6 out of 17 patients (35%) with ulcerative colitis. Both in the patient samples and in the 1000 genomes project, the two SNPs were found to co-occur whenever present (D' = 1). PMID:26681582

  15. Wireless capsule video endoscopy:Three years of experience

    Rami Eliakim

    2004-01-01

    AIM: To review and summerize the current literatue regarding M2A wireless capsule endoscopy.METHODS: Peer reviewed publications regarding the use of capsule endoscopy as well as our personal experience were reviewed.RESULTS: Review of the literature dearly showed that capsule endoscopy was superior to enteroscopy, small bowel follow through and computerized tomography in patients with obscure gastrointestinal bleeding, iron deficiency anemia,or suspected Crohn′s disease. It was very sensitive for the diagnosis of small bowel tumors and for survailance of small bowel pathology in patients with Gardner syndrome or familial adenomatous polyposis syndrome. Its role in celiac disease and in patients with known Crohn′s disease was currently being investigated.CONCLUSION: Capsule video endoscopy is a superior and more sensitive diagnostic tool than barium follow through,enteroscopy and entero- CT in establishing the diagnosis of many small bowel pathologies.

  16. Frequency of Thyroid Nodules among Patients with Colonic Polyps

    Cevdet Duran

    2012-01-01

    Full Text Available Aim. Colonic polyps and thyroid nodules are common diseases and their frequency increases with age. In the literature, there is no study investigating the coexistence of colonic polyps and thyroid nodules. Therefore, this study was designed to investigate thyroid nodule prevalence in patients with colonic polyps. Material and Methods. Sixty-six patients with colonic polyps and 146 patients without colonic polyps enrolled into the study. Age and sex matched control group was composed from patients without colonic polyps. Colonoscopic examinations, thyroid ultrasonographies were performed in all patients, and TSH were measured. Results. Male/female ratio in polyp and control groups were 40/26 versus 68/78, respectively (P=0.058. Mean ages were similar in both groups (53.3±11.4 versus, 51.8±11.4, P=0.373. Thyroid nodule was detected in 44 (66.7% patients with polyps and in 61 (41.8% controls (P=0.001. Patients with adenomatous polyps had 5 or more thyroid nodules compared to patients with hyperplastic polyps (P=0.03. Thyroid nodules were more prevalent among patients aged 50 or older compared to 50 years or less (P=0.023. Conclusion. Thyroid nodules were detected more common in patients with colonic polyps. Further studies are needed to clarify this coexistence.

  17. Primary Adenocarcinoma of Ileostomy: Case Report with Review of the Literature

    Shailesh Mohandas

    2010-01-01

    Full Text Available Primary adenocarcinoma is a rare and late complication following proctocolectomy and ileostomy for ulcerative colitis, familial adenomatous polyposis, Crohn's disease and multifocal colorectal cancer. We report a case of adenocarcinoma of the ileostomy occurring 48 years after proctocolectomy for ulcerative colitis. A review of the literature suggests that there are 39 cases reported in literature and this case reports the longest interval between formation of ileostomy and diagnosis of ileostomy adenocarcinoma. This case also reports lymph node metastasis to the adjacent mesenteric lymph node. The incidence of lymphnode metastasis is 15 percent as per literature. Onces diagnosis is confirmed by biopsy enblock excision with or without stomal relocation is the main stay of treatment. Patient education and regular surveillance of patients with long-standing ileostomy is recommended for early detection of this unusual cancer.

  18. A large abdominal desmoid tumour associated with pregnancy and puerperium

    Setu Rathod

    2014-02-01

    Full Text Available We report a rare case of huge abdominal desmoid tumour first detected during pregnancy. The patient delivered vaginally and the size of the tumour increased during puerperium for which resection was done. Most of these tumours occur in the abdominal muscles particularly right rectus abdominis, perhaps related to trauma from abdominal stretching and movement. These tumours are known to regress spontaneously after delivery which was not in our case. Subsequent pregnancies do not appear to result in recurrence in either FAP (Familial Adenomatous Polyposis or non-FAP patients. It is not clear from currently available data whether pregnancy associated desmoids are molecularly distinct from other desmoids. [Int J Reprod Contracept Obstet Gynecol 2014; 3(1.000: 270-272

  19. A Comparison Between Denaturing Gradient Gel Electrophoresis and Denaturing High Performance Liquid Chromatography in Detecting Mutations in Genes Associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC and the Identification of 9 New Mutations Previously Unidentified by DGGE

    Meldrum Cliff J

    2003-12-01

    Full Text Available Abstract Denaturing high performance liquid chromatography is a relatively new method by which heteroduplex structures formed during the PCR amplification of heterozygote samples can be rapidly identified. The use of this technology for mutation detection in hereditary non-polyposis colorectal cancer (HNPCC has the potential to appreciably shorten the time it takes to analyze genes associated with this disorder. Prior to acceptance of this method for screening genes associated with HNPCC, assessment of the reliability of this method should be performed. In this report we have compared mutation and polymorphism detection by denaturing gradient gel electrophoresis (DGGE with denaturing high performance liquid chromatography (DHPLC in a set of 130 families. All mutations/polymorphisms representing base substitutions, deletions, insertions and a 23 base pair inversion were detected by DHPLC whereas DGGE failed to identify four single base substitutions and a single base pair deletion. In addition, we show that DHPLC has been used for the identification of 5 different mutations in exon 7 of hMSH2 that could not be detected by DGGE. From this study we conclude that DHPLC is a more effective and rapid alternative to the detection of mutations in hMSH2 and hMLH1 with the same or better accuracy than DGGE. Furthermore, this technique offers opportunities for automation, which have not been realised for the majority of other methods of gene analysis.

  20. Surveillance of FAP: a prospective blinded comparison of capsule endoscopy and other GI imaging to detect small bowel polyps

    Tescher Paul

    2010-04-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is a hereditary disorder characterized by polyposis along the gastrointestinal tract. Information on adenoma status below the duodenum has previously been restricted due to its inaccessibility in vivo. Capsule Endoscopy (CE may provide a useful adjunct in screening for polyposis in the small bowel in FAP patients. This study aims to evaluate the effectiveness of CE in the assessment of patients with FAP, compared to other imaging modalities for the detection of small bowel polyps. Method 20 consecutive patients with previously diagnosed FAP and duodenal polyps, presenting for routine surveillance of polyps at The Royal Melbourne Hospital were recruited. Each fasted patient initially underwent a magnetic resonance image (MRI of the abdomen, and a barium small bowel follow-through study. Capsule Endoscopy was performed four weeks later on the fasted patient. An upper gastrointestinal side-viewing endoscopy was done one (1 to two (2 weeks after this. Endoscopists and investigators were blinded to results of other investigations and patient history. Results Within the stomach, upper gastrointestinal endoscopy found more polyps than other forms of imaging. SBFT and MRI generally performed poorly, identifying fewer polyps than both upper gastrointestinal and capsule endoscopy. CE was the only form of imaging that identified polyps in all segments of the small bowel as well as the only form of imaging able to provide multiple findings outside the stomach/duodenum. Conclusion CE provides important information on possible polyp development distal to the duodenum, which may lead to surgical intervention. The place of CE as an adjunct in surveillance of FAP for a specific subset needs consideration and confirmation in replication studies. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12608000616370

  1. APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane

    Mills, Kate M.; Brocardo, Mariana G.; Henderson, Beric R.

    2016-01-01

    The role of adenomatous polyposis coli (APC) tumor suppressor at mitochondria is unclear. We show that APC associates with the Miro/Milton/kinesin complex to stimulate anterograde transport of mitochondria. This identifies the first regulatory role of APC in organelle transport. APC cancer mutations block this activity.

  2. The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer : Genetic Association Study in 18,723 Individuals

    Abuli, Anna; Bujanda, Luis; Munoz, Jenifer; Buch, Stephan; Schafmayer, Clemens; Maiorana, Maria Valeria; Veneroni, Silvia; van Wezel, Tom; Liu, Tao; Westers, Helga; Esteban-Jurado, Clara; Ocana, Teresa; Pique, Josep M.; Andreu, Montserrat; Jover, Rodrigo; Carracedo, Angel; Xicola, Rosa M.; Llor, Xavier; Castells, Antoni; Dunlop, Malcolm; Hofstra, Robert; Lindblom, Annika; Wijnen, Juul; Peterlongo, Paolo; Hampe, Jochen; Ruiz-Ponte, Clara; Castellvi-Bel, Sergi

    2014-01-01

    Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly

  3. Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer

    Dow, Lukas E; O'Rourke, Kevin P; Simon, Janelle; Tschaharganeh, Darjus F; van Es, Johan H; Clevers, Hans; Lowe, Scott W

    2015-01-01

    The adenomatous polyposis coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally su

  4. Análise imuno-histoquímica das citoqueratinas em ameloblastoma e tumor odontogênico adenomatóide Immunohistochemical analysis of cytokeratins in ameloblastoma and adenomatoid odontogenic tumor

    Fernanda Ferreira Lopes

    2005-12-01

    Full Text Available OBJETIVO: O presente trabalho teve por objetivo traçar o perfil das citoqueratinas (CKs 7, 8, 10, 13, 14, 18 e 19 em ameloblastomas e tumor odontogênico adenomatóide (TOA visando contribuir para o entendimento da histogênese desses tumores e somar com os resultados já relatados na literatura. MATERIAL E MÉTODO: do arquivo do Laboratório de Anatomia Patológica do Departamento de Odontologia da Universidade Federal do Rio Grande do Norte (UFRN foi selecionada uma amostra com dez casos de ameloblastomas e oito de TOA para o estudo imuno-histoquímico, utilizando-se anticorpos anti-CKs pelo método da estreptoavidina-biotina. RESULTADOS: Observou-se que nos ameloblastomas a CK 14 esteve presente em todos os casos, enquanto a CK 19 foi observada nas células periféricas (oito casos e nas centrais (cinco casos. Para os TOA, observou-se imunopositividade para a CK 14 em todos os casos, enquanto a CK 19 esteve marcada predominantemente nas células ductais (seis casos. CONCLUSÃO: As citoqueratinas são expressas de forma variada nos ameloblastomas e nos TOA, os quais preservam CK típicas do germe dental em estágios avançados do desenvolvimento, confirmando sua origem exclusiva a partir do epitélio odontogênico e não se evidenciando CK características do epitélio escamoso.OBJECTIVES: The aim of the present study was to describe the immunohistochemical expression of cytokeratins (CKs 7, 8, 10,13, 14, 18 and 19 in the epithelial components of ameloblastomas and adenomatoid odontogenic tumor (AOT. The results were compared and histogenesis discussed. MATERIAL AND METHOD: Specimens of ten ameloblastomas and eight adenomatoid odontogenic tumors were examined by immunohistochemistry using streptavidin-biotin-peroxidase complex method and anti-CKs antibody. The sample was obtained from Department of Oral Pathology, Federal University of Rio Grande do Norte. RESULTS: Immunohistochemical reactivity for CK14 was detected in all cases of

  5. Adenocarcinoma arising at ileostomy sites: Two cases and areview of the literature

    2015-01-01

    Total colectomy with ileostomy placement is a treatmentfor patients with inflammatory bowel disease orfamilial adenomatous polyposis (FAP). A rare and latecomplication of this treatment is carcinoma arisingat the ileostomy site. We describe two such cases a78-year-old male 30 years after subtotal colectomy andileostomy for FAP, and an 85-year-old male 50 yearsafter colectomy and ileostomy for ulcerative colitis. Thelong latency period between creation of the ileostomiesand development of carcinoma suggests a chronicmetaplasia due to an irritating/inflammatory causativefactor. Surgical excision of the mass and relocation ofthe stoma is the mainstay of therapy, with possiblebenefits from adjuvant chemotherapy. Newly developedlesions at stoma sites should be biopsied to rule out thepossibility of this rare ileostomy complication.

  6. Rapid detection of most frequent Slovenian germ-line mutations in BRCA1 gene using real-time PCR and melting curve analysis

    Background. Detection of inherited mutations in cancer susceptibility genes is of great importance in some types of cancers including the colorectal cancer (mutations of APC gene in familial adenomatous polyposis - FAP, mutations in mismatch repair genes in hereditary nonpolyposis colorectal cancer - HNPCC), malignant melanoma (mutations in CDKN2A and CDK4 genes) and breast cancer (mutations in BRCA1 and BRCA2 genes). Methods. This article presents the technical data for the detection of five mutations in BRCA1 gene in breast cancer patients and their relatives. The mutations - 1806C>T, 300T>G, 300T>A, 310G>A, 5382insC - were determined by the real-time PCR and the melting curve analysis. Results and conclusion. In comparison to direct sequencing, this method proved to be sensitive and rapid enough for the routine daily determination of mutations in DNA isolated from the peripheral blood. (author)

  7. How I do it: the stapled ileal J pouch at restorative proctocolectomy.

    Martin, S T

    2011-12-01

    Ileal pouch-anal anastomosis (IPAA) following proctocolectomy is the preferred option for patients with medically refractory ulcerative colitis, indeterminate colitis, and familial adenomatous polyposis. However, it remains a procedure associated with morbidity and mortality. Pelvic sepsis, pouch fistulae, and anastomotic dehiscence predispose to pouch failure. We report our experience with an adaptation for the formation of the stapled ileal J pouch using the GIA™ 100 stapling device (Covidien, Mansfield, Massachusetts, USA). When creating the J pouch, we remove the bevelled plastic protector from the thin fork of the stapling device, allowing the staple line to be completed to the tip of the stapled efferent limb of the pouch, thereby minimizing potential blind ending in the efferent limb and injury to the transverse staple line.

  8. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

    Christopher S. Williams

    1999-06-01

    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  9. Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

    Canney, A

    2012-02-01

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

  10. The Prevalence of Allergic Rhinitis in Patients with Chronic Rhinosinusitis

    Mehdi Bakhshaee

    2014-10-01

    Full Text Available Introduction: Chronic rhinosinusitis (CRS is a multifactorial disease. Allergies are considered a predisposing factor to CRS; however, this remains controversial. The objective of this research was to investigate the prevalence of co-morbidities and allergic reaction, and to specify the most common allergens in patients with confirmed CRS.   Materials and Methods: One hundred patients with signs and symptoms of CRS who met the diagnostic endoscopic and radiologic criteria of chronic rhinosinusitis were selected. They filled out a questionnaire and underwent a skin prick test for the common inhalant allergens. Allergic rhinitis was diagnosed according to the history and positive skin prick tests.   Results: The mean age of patients was 34. Males were slightly more involved (54%. The prevalence of polypoid and none-polypoid rhinosinusitis was 54% and 46% respectively. The patients’ most common symptoms were nasal discharge (95%, blockage (94%, smell disorders (63%, cough (45%, halitosis (41%, lethargy (37%, and aural fullness (36%. Allergy to at least one allergen was noted in 64% of the CRS patients which is higher than general population in Mashhad, Iran with allergic rhinitis (22.4%. Salsola was the most common allergen. There was no significant difference in allergic reactions between polypoid and non-polypoid CRS patients.   Conclusion:  Allergic reactions was found in Iranian CRS patients with or without polyposis to be much higher than general population in Mashhad with allergic rhinitis alone.

  11. Extensive metabolic disorders are present in APC(min) tumorigenesis mice.

    Liu, Zhenzhen; Xiao, Yi; Zhou, Zhengxiang; Mao, Xiaoxiao; Cai, Jinxing; Xiong, Lu; Liao, Chaonan; Huang, Fulian; Liu, Zehao; Ali Sheikh, Md Sayed; Plutzky, Jorge; Huang, He; Yang, Tianlun; Duan, Qiong

    2016-05-15

    Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of β-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. PMID:26948948

  12. Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma

    Gian Paolo Fadini

    2011-01-01

    Full Text Available We describe an unusual case of hypoglycemic syndrome in a 69-year old woman with a proinsulin-only secreting pancreatic endocrine adenoma. The clinical history was highly suggestive of an organic hypoglycemia, with normal or relatively low insulin concentrations and elevated proinsulin levels. Magnetic resonance and computed tomography of the abdomen showed a 1 cm pancreatic nodule and multiple accessory spleens. The diagnosis was confirmed by selective angiography, showing location and vascularization of the nodule, despite no response to intra-arterial calcium. After resection, the hypoglycemic syndrome resolved. The surgical specimen was comprised of a neuroendocrine adenomatous tissue with high proinsulin immunoreactivity. Study of this unusual case of proinsulinoma underlines (i the need to assay proinsulin in patients with hypoglycemia and normal immunoreactive insulin, (ii the differential diagnosis in the presence of accessory spleens, (iii the unresponsiveness to intra-arterial calcium stimulation, and (iv the extensive evaluation needed to reach a final diagnosis.

  13. Possible role of EMID2 on nasal polyps pathogenesis in Korean asthma patients

    Pasaje Charisse Flerida

    2012-01-01

    Full Text Available Abstract Background Since subepithelial fibrosis and protruded extracellular matrix are among the histological characteristics of polyps, the emilin/multimerin domain-containing protein 2 (EMID2 gene is speculated to be involved in the presence of nasal polyps in asthma and aspirin-hypersensitive patients. Methods To investigate the association between EMID2 and nasal polyposis, 49 single-nucleotide polymorphisms (SNPs were genotyped in 467 asthmatics of Korean ancestry who were stratified further into 114 aspirin exacerbated respiratory disease (AERD and 353 aspirin-tolerant asthma (ATA subgroups. From pairwise comparison of the genotyped polymorphisms, 14 major haplotypes (frequency > 0.05 were inferred and selected for association analysis. Differences in the frequency distribution of EMID2 variations between polyp-positive cases and polyp-negative controls were determined using logistic analyses. Results Initially, 13 EMID2 variants were significantly associated with the presence of nasal polyps in the overall asthma group (P = 0.0008-0.05, OR = 0.54-1.32 using various modes of genetic inheritance. Although association signals from 12 variants disappeared after multiple testing corrections, the relationship between EMID2_BL1_ht2 and nasal polyposis remained significant via a codominant mechanism (Pcorr = 0.03. On the other hand, the nominal associations observed between the genetic variants tested for the presence of nasal polyps in AERD (P = 0.003-0.05, OR = 0.25-1.82 and ATA (P = 0.01-0.04, OR = 0.46-10.96 subgroups disappeared after multiple comparisons, suggesting lack of associations. Conclusions These preliminary findings suggest that EMID2_BL1_ht2 may be a susceptibility marker of inflammation of the nasal passages among Korean asthma patients.

  14. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Ann-Marie Baker

    2014-08-01

    Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

  15. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Baker, Ann-Marie; Cereser, Biancastella; Melton, Samuel; Fletcher, Alexander G.; Rodriguez-Justo, Manuel; Tadrous, Paul J.; Humphries, Adam; Elia, George; McDonald, Stuart A.C.; Wright, Nicholas A.; Simons, Benjamin D.; Jansen, Marnix; Graham, Trevor A.

    2014-01-01

    Summary Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+). Furthermore, we show that, in adenomatous crypts (APC−/−), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics. PMID:25127143

  16. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth.

    Elias Gounaris

    Full Text Available It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than (3/4 of the probe signal was localized in CD11b(+Gr1(+ myeloid derived suppressor cells (MDSC and CD11b(+F4/80(+ macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFalpha in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.

  17. JP-HHT phenotype in Danish patients with SMAD4 mutations.

    Jelsig, A M; Tørring, P M; Kjeldsen, A D; Qvist, N; Bojesen, A; Jensen, U B; Andersen, M K; Gerdes, A M; Brusgaard, K; Ousager, L B

    2016-07-01

    Patients with germline mutations in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT): the JP-HHT syndrome. The complete phenotypic picture of this syndrome is only just emerging. We describe the clinical characteristics of 14 patients with SMAD4-mutations. The study was a retrospective, register-based study. SMAD4 mutations carriers were identified through the Danish HHT-registry, the genetic laboratories - and the genetic departments in Denmark. The medical files from relevant departments were reviewed and symptoms of HHT, JPS, aortopathy and family history were noted. We detected 14 patients with SMAD4 mutations. All patients had polyps removed and 11 of 14 fulfilled the diagnostic criteria for JPS. Eight patients were screened for HHT-symptoms and seven of these fulfilled the Curaçao criteria. One patient had aortic root dilation. Our findings support that SMAD4 mutations carriers have symptoms of both HHT and JPS and that the frequency of PAVM and gastric involvement with polyps is higher than in patients with HHT or JPS not caused by a SMAD4 mutation. Out of eight patients screened for aortopathy, one had aortic root dilatation, highlighting the need for additional screening for aortopathy. PMID:26572829

  18. Influence of perception of colorectal cancer risk and patient bowel preparation behaviors: a study in minority populations

    Gaduputi V

    2015-01-01

    Full Text Available Vinaya Gaduputi, Chaitanya Chandrala, Hassan Tariq, Sailaja Sakam, Anil Dev, Sridhar Chilimuri Bronx Lebanon Hospital Center, Department of Medicine, Bronx, New York, NY, USA Background: Large disparities exist in the utilization rates of screening modalities for colorectal cancer (CRC in different socioeconomic areas. In this study, we evaluated whether the quality of bowel preparation differed significantly among populations with a high risk of CRC compared with that among the general population after matching for potential confounding factors.Methods: Hispanic and African American patients who underwent routine screening or surveillance colonoscopies in an outpatient setting between 2003 and 2013 were included in this retrospective study. Patients who underwent colonoscopies for emergent indications and repeat routine screening colonoscopies because of prior history of inadequate bowel preparation were excluded from this study. The patients were divided into three groups: patients having an average risk of being diagnosed with CRC (group 1; patients having a high risk of being diagnosed with CRC because of a personal history of adenomatous polyps (group 2; and patients having a high risk of being diagnosed with CRC because of a family history of CRC in first-degree relatives (group 3. All the patients were given preprocedural counseling and written instructions for bowel preparation. Data on demographic information, method of bowel preparation, quality of bowel preparation, comorbidities, and prescription medications were collected.Results: In all, 834 patients had a "high-risk for CRC" surveillance colonoscopy in view of their personal history of adenomatous polyps and were included in group 2. In total, 250 patients had a "high-risk for CRC" screening colonoscopy in view of their family history of CRC in first-degree relatives and were included in group 3. Further, 1,000 patients were selected to serve as controls (after matching for age

  19. Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

    Kast Karin

    2012-11-01

    Full Text Available Abstract Background Hereditary Breast and Ovarian Cancer Syndrome (HBOCS and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR genes MLH1, MSH2, MSH6 or PMS2 are very rare. Case presentation We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Conclusions Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

  20. Cytokine profile of nasal and middle ear polyps in a patient with Woakes' syndrome and eosinophilic otitis media.

    De Loof, Marie; De Leenheer, Els; Holtappels, Gabriële; Bachert, Claus

    2016-01-01

    Woakes' syndrome is characterised by severe recurrent nasal polyps in early childhood with broadening of the nose, nasal dyscrinia, frontal sinus aplasia and bronchiectasis. Eosinophilic otitis media (EOM) is an intractable condition that can cause gradual or sudden deterioration of hearing and is associated with comorbid asthma. For these reasons, both diseases must be recognised and treated appropriately. We present a case of a 20-year-old man with Woakes' syndrome complicated by EOM, with polyps in both middle ears; this condition has so far not been described as an entity of eosinophilic disease in the literature. We have, from reviewing the literature, learned that this is the first time that results of tissue examination on nasal polyposis with respect to tissue IgE, eosinophil-cationic protein, interleukin (IL)-17 and IL-5 in a patient with Woakes' syndrome and EOM, has been reported and discussed. PMID:27143164

  1. Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

    Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes

  2. Quality of life after ileal pouch-anal anastomosis: an evaluation of diet and other factors using the Cleveland Global Quality of Life instrument.

    Coffey, J C

    2012-02-03

    PURPOSE: Although functional results after ileal pouch-anal anastomosis are excellent, imperfections of function do occur. In this setting, quality-of-life assessment is an invaluable tool in determining overall therapeutic efficacy. We evaluated the impact of dietary restrictions, preoperative diagnosis (ulcerative colitis vs. familial adenomatous polyposis), and pregnancy (after pouch insertion) on quality of life. METHODS: After ethical approval, 64 patients were reviewed (mean age, 31 (range, 15-54) years). Long-term quality of life in patients after ileal pouch-anal anastomosis was assessed using the Cleveland Global Quality of Life instrument or Fazio score. The Cleveland Global Quality of Life score is a novel quality-of-life instrument specifically designed for patients with ileal pouches. Stool frequency and continence were recorded to establish the functional status of this group. RESULTS: Sixty-one patients (95.3 percent) complained of some form of dietary restriction and adopted a fixed dietary regimen. All such patients felt that a breach of this regimen would impinge significantly on their quality of life. Late eating and alcohol were associated with diarrhea, whereas smoking was not. Constipation was infrequently reported. The mean Cleveland Global Quality of Life score of patients with ulcerative colitis (0.81 +\\/- 0.13) was greater than that of patients with ulcerative colitis and a background of pouchitis (0.78 +\\/- 0.16; P = 0.042). Whereas postoperative stool frequency in patients with familial adenomatous polyposis was always higher than the preoperative level (4 vs. 2 movements per day; P = 0.04), the Cleveland Global Quality of Life score of this group was lower than that of ulcerative colitis patients (0.77 vs. 0.81; P = 0.047). The Cleveland Global Quality of Life score of females who had had pregnancies after pouch formation was 0.70, significantly lower (P = 0.039) than that of ulcerative colitis patients, although pouch function was

  3. Manuseio de grave diminuição de hemoglobina em paciente jovem, testemunha de Jeová, submetido à proctocolectomia total: relato de caso Manoseo de grave disminución de hemoglobina en paciente joven, testigo de Jehová, sometido a la proctocolectomia total: relato de caso Extreme intraoperative hemodilution in Jehovah’s witness patient submitted total proctocolectomy: case report

    Luiz Eduardo Imbelloni

    2005-10-01

    family history of adenomatous polyposis. The disease was manifested at eight years of age, characterized by bleeding. At 13 years of age he was submitted to total colectomy. At 17 years of age he was submitted to total proctocolectomy. Patient was prepared with erythropoietin, folic acid, infusion of iron and vitamin B12. Red blood cell count revealed He = 4,200,000/mm³, hemoglobin = 10.5 g/dL, hematocrit = 37% platelets = 273,000/mm³ and normal prothrombin time. Patient was continuously monitored with NIBP, pulse oximetry, capnography and ECG. Anesthesia was induced with propofol, sufentanil, pancuronium and enflurane in closed system. Patient received 7,000 mL lactated Ringer’s and 150 mL of 20% human albumin. Total diuresis was 2,900 mL. Surgery lasted 10 hours and 30 minutes. Patient was referred to the ICU with 20% hematocrit, 2,300,000/mm³ red cells, 4,2 g/dL hemoglobin and was maintained with propofol and atracurium. Next day evaluation revealed 18% hematocrit, 2,050,000/mm³ red cells and 4 g/dL hemoglobin. Patient was extubated 18 hours after surgery and was referred to the ward. Patient started eating four days after surgery and was discharged the 10th postoperative day. Thirty days later patient presented 35% hematocrit, 4,000,000/mm³ red cells and 9.5 g/dL hemoglobin. Six months later he returned for ileostomy closing. Patient was submitted to 12 surgeries without a single blood transfusion. CONCLUSIONS: A good planning of the whole team (clinician, surgeon, anesthesiologist, intensive care staff allows us to perform surgical procedures associated to major blood losses without administering blood.

  4. Low red blood cell levels of deglycating enzymes incolorectal cancer patients

    Maria Notarnicola; Maria Gabriella Caruso; Valeria Tutino; Vito Guerra; Giovanni Misciagna

    2011-01-01

    AIM: To investigate Glyoxalase Ⅰ and fructosamine-3- kinase (FN3K) activity in red blood cells from patients with colorectal adenomas and cancer.METHODS: Thirty three consecutive subjects with one or more histologically confirmed colorectal adenomatous polyps, 16 colorectal cancer patients and a group of 11 control subjects with normal colonoscopy were included in the study. Glyoxalase Ⅰ and FN3K activities were measured in red blood cells using a spectrophotometric and radiometric assay, respectively.RESULTS: A significant reduction in both Glyoxalase Ⅰ and FN3K activity was detected in patients with tumors compared to patients with adenomas and the controls. Erythrocyte Glyoxalase Ⅰ activity in colorectal cancer was approximately 6 times lower than that detected in patients with adenoma (0.022 ± 0.01 mmol/min per milliliter vs 0.128 ± 0.19 mmol/min per milliliter of red blood cells, P = 0.003, Tukey's test). FN3K activity in red blood cells from patients with colon cancer was approximately 2 times lower than that detected in adenomapatients (19.55 ± 6.4 pmol/min per milliliter vs 38.6 ± 31.7 pmol/min per milliliter of red blood cells, P = 0.04, Tukey's test).CONCLUSION: These findings suggest that deglycating enzymes may be involved in the malignant transformation of colon mucosa.

  5. Treatment of nasal polyposis in Byzantine times.

    Lascaratos, J G; Segas, J V; Assimakopoulos, D A

    2000-09-01

    The goal of this study was to describe the therapeutic methods and surgical techniques used during Byzantine times (AD 324-1453) for a disease that has occupied physicians since antiquity: nasal polyps. The original Greek-language texts of the Byzantine medical writers, most of which were published after the 17th century, were studied in order to identify the early knowledge of the definition, symptoms, conservative treatments, and surgical intervention in cases of this disease. A considerable number of conservative treatments, etiologic and local (with inunctions or blowing of caustic substances), with evident influence from Roman medicine, were identified even in the early Byzantine medical texts (4th century). Further, some surgical techniques were described that seem to constitute evolution of the Hippocratic tradition. From the study of the original texts of Byzantine medical writers, their interest in the rhinological diseases is evident; in the case of nasal polyps, new techniques were mentioned. The first meticulous intranasal surgical removal of polyps was described. These techniques, obviously developed during the Hellenistic period, initially influenced European medicine and later the rest of the world. PMID:11007093

  6. Genetics Home Reference: juvenile polyposis syndrome

    ... of particular genes and the growth and division (proliferation) of cells. Mutations in the BMPR1A gene or the SMAD4 ... with their roles in regulating gene activity and cell proliferation. This lack of regulation causes cells to grow ...

  7. AXIN1 and AXIN2 Variants in Gastrointestinal Cancers

    Serina M. Mazzoni; Fearon, Eric R.

    2014-01-01

    Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and ...

  8. Diagnostic accuracy and tolerability of contrast enhanced CT colonoscopy in symptomatic patients with increased risk for colorectal cancer

    Ozsunar, Yelda [Department of Radiology, School of Medicine, Adnan Menderes University, Aydin (Turkey)], E-mail: yozsunar@adu.edu.tr; Coskun, Guelten [Izmir Ataturk Egitim ve Arastirma Hastanesi, Izmir (Turkey); Delibas, Naciye; Uz, Burcin [Department of Radiology, School of Medicine, Adnan Menderes University, Aydin (Turkey); Yuekselen, Vahit [Department of Gastroenterology, School of Medicine, Adnan Menderes University, Aydin (Turkey)

    2009-09-15

    Objective: We compared the accuracy and tolerability of intravenous contrast enhanced spiral computed tomography colonography (CTC) and optical colonoscopy (OC) for the detection of colorectal neoplasia in symptomatic patients for colorectal neoplasia. Methods: A prospective study was performed in 48 patients with symptomatic patients with increased risk for colorectal cancer. Spiral CTC was performed in supine and prone positions after colonic cleansing. The axial, 2D MPR and virtual endoluminal views were analyzed. Results of spiral CTC were compared with OC which was done within 15 days. The psychometric tolerance test was asked to be performed for both CTC and colonoscopy after the procedure. Results: Ten lesions in 9 of 48 patients were found in CTC and confirmed with OC. Two masses and eight polyps, consisted of 1 tubulovillous, 1 tubular, 2 villous adenoma, 4 adenomatous polyp, 4 adenocarcinoma, were identified. Lesion prevalence was 21%. Sensitivity, specificity, accuracy, positive and negative predictive values were found 100%, 87%, 89%, 67% and 100%, respectively. Psychometric tolerance test showed that CTC significantly more comfortable comparing with OC (p = 0.00). CTC was the preferred method in 37% while OC was preferred in 6% of patients. In both techniques, the most unpleasant part was bowel cleansing. Conclusion: Contrast enhanced CTC is a highly accurate method in detecting colorectal lesions. Since the technique was found to be more comfortable and less time consuming compare to OE, it may be preferable in management of symptomatic patients with increased risk for colorectal cancer.

  9. Diagnostic accuracy and tolerability of contrast enhanced CT colonoscopy in symptomatic patients with increased risk for colorectal cancer

    Objective: We compared the accuracy and tolerability of intravenous contrast enhanced spiral computed tomography colonography (CTC) and optical colonoscopy (OC) for the detection of colorectal neoplasia in symptomatic patients for colorectal neoplasia. Methods: A prospective study was performed in 48 patients with symptomatic patients with increased risk for colorectal cancer. Spiral CTC was performed in supine and prone positions after colonic cleansing. The axial, 2D MPR and virtual endoluminal views were analyzed. Results of spiral CTC were compared with OC which was done within 15 days. The psychometric tolerance test was asked to be performed for both CTC and colonoscopy after the procedure. Results: Ten lesions in 9 of 48 patients were found in CTC and confirmed with OC. Two masses and eight polyps, consisted of 1 tubulovillous, 1 tubular, 2 villous adenoma, 4 adenomatous polyp, 4 adenocarcinoma, were identified. Lesion prevalence was 21%. Sensitivity, specificity, accuracy, positive and negative predictive values were found 100%, 87%, 89%, 67% and 100%, respectively. Psychometric tolerance test showed that CTC significantly more comfortable comparing with OC (p = 0.00). CTC was the preferred method in 37% while OC was preferred in 6% of patients. In both techniques, the most unpleasant part was bowel cleansing. Conclusion: Contrast enhanced CTC is a highly accurate method in detecting colorectal lesions. Since the technique was found to be more comfortable and less time consuming compare to OE, it may be preferable in management of symptomatic patients with increased risk for colorectal cancer.

  10. Management of the patient with eosinophilic asthma: a new era begins

    Jantina C. de Groot

    2015-09-01

    Full Text Available Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion, typical lung function abnormalities (“fixed” airflow obstruction, reduced forced vital capacity and increased residual volume, typical comorbidities (nasal polyposis and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.

  11. Colectomy in a patient with pneumatosis coli

    Karlsen, Stine; Bregendahl, Sidse; Tøttrup, Anders;

    2014-01-01

    Pneumatosis coli (PC) is a rare condition which may be difficult to diagnose. We report a case of PC in a 46-year-old woman, where colonoscopy and biopsies showed signs of widespread polyposis. She had a prophylactic colectomy. Pathologic examination of the specimen showed multiple air-filled cysts...

  12. Psychosocial outcome following genetic risk counselling for familial colorectal cancer. A comparison of affected patients and family members.

    Keller, M; Jost, R; Haunstetter, C M; Sattel, H; Schroeter, C; Bertsch, U; Cremer, F; Kienle, P; Tariverdian, M; Kloor, M; Gebert, J; Brechtel, A

    2008-11-01

    Few studies have reported prospective data on psychosocial outcomes after genetic counselling in families with suspected hereditary non-polyposis colorectal cancer (HNPCC). This prospective study examines the impact of multidisciplinary risk counselling on the psychosocial outcome of 139 affected cancer patients and 233 family members without cancer at risk for HNPCC. Participants completed questionnaires specific to HNPCC before and 8 weeks after attending the familial cancer clinic. Affected patients' levels of distress were closely related to their health status and exceeded that of unaffected individuals, as did worry regarding their relatives' risk. A significant reduction in general anxiety (Hospital Anxiety and Depression Scale), distress specific to familial CRC (Impact of Events Scale) and general cancer worry (Distress Hereditary Disorder) was demonstrated after counselling in both affected patients and unaffected individuals. Reduction in distress was more pronounced in affected patients given a high risk of HNPCC compared with those at intermediate risk. Among unaffected individuals, distress declined regardless of what clinical risk they were assigned. Their perceptions of risk and cancer-related threat declined, while confidence in effective surveillance increased. These results suggest the beneficial effects of multidisciplinary counselling even when high-risk information is conveyed. A patient's previous cancer experience is likely to contribute to clinically relevant distress (15% of those patients), indicating the need for appropriate counselling. PMID:18954412

  13. Targeting the DNA replication checkpoint by pharmacologic inhibition of Chk1 kinase: a strategy to sensitize APC mutant colon cancer cells to 5-fluorouracil chemotherapy

    Martino-Echarri, Estefania; Henderson, Beric R.; Brocardo, Mariana G.

    2014-01-01

    5-fluorouracil (5-FU) is the first line component used in colorectal cancer (CRC) therapy however even in combination with other chemotherapeutic drugs recurrence is common. Mutations of the adenomatous polyposis coli (APC) gene are considered as the initiating step of transformation in familial and sporadic CRCs. We have previously shown that APC regulates the cellular response to DNA replication stress and recently hypothesized that APC mutations might therefore influence 5-FU resistance. T...

  14. The ins and outs of APC and β-catenin nuclear transport

    Henderson, Beric R.; Fagotto, Francois

    2002-01-01

    Adenomatous polyposis coli (APC) and β-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a β-catenin chaperone. Here, we review the regulation of APC and β-catenin subcellular localization, in particular in cancer cells. ...

  15. Redefining the subcellular location and transport of APC: new insights using a panel of antibodies

    Brocardo, Mariana; Näthke, Inke S.; Henderson, Beric R.

    2005-01-01

    Adenomatous polyposis coli (APC) is a tumour suppressor involved in colon cancer progression. We and others previously described nuclear–cytoplasmic shuttling of APC. However, there are conflicting reports concerning the localization of endogenous wild-type and tumour-associated, truncated APC. To resolve this issue, we compared APC localization using immunofluorescence (IF) microscopy and cell fractionation with nine different APC antibodies. We found that three commonly used APC antibodies ...

  16. Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization

    Piao, Meiyu; Cao, Hailong; He, Nana; Yang, Boli; Dong, Wenxiao; Xu, Mengque; Yan, Fang; Zhou, Bing; Wang, Bangmao

    2016-01-01

    Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks. Primary macrophages were isolated; after berberine treatment, the change in signaling cascade wa...

  17. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene

    Martínez, María Elena; O'Brien, Thomas G.; Fultz, Kimberly E.; Babbar, Naveen; Yerushalmi, Hagit; Qu, Ning; Guo, Yongjun; Boorman, David; Einspahr, Janine; Alberts, David S.; Gerner, Eugene W.

    2003-01-01

    Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between t...

  18. Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation

    Yaser Atlasi; Rubina Noori; Claudia Gaspar; Patrick Franken; Andrea Sacchetti; Haleh Rafati; Tokameh Mahmoudi; Charles Decraene; Calin, George A; Merrill, Bradley J.; Riccardo Fodde

    2013-01-01

    Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and endodermal lineages. However, the underlying molecular and cellular mechanisms through which Wnt regulates lineage differentiation in mouse ES...

  19. Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling

    Roberts, David M.; Pronobis, Mira I.; Poulton, John S; Waldmann, Jon D.; Stephenson, Elise M.; Hanna, Shahnaz; Peifer, Mark

    2011-01-01

    Negatively regulating signaling by targeting key effectors for ubiquitina­tion/destruction is essential for development and oncogenesis. The tumor suppressor adenomatous polyposis coli (APC), an essential negative regulator of Wnt signaling, provides a paradigm. APC mutations occur in most colon cancers. Acting in the “destruction complex” with Axin, glycogen synthase kinase 3, and casein kinase, APC targets ßcatenin (ßcat) for phosphorylation and recognition by an E3 ubiquitin-ligase. Despit...

  20. Wnt/beta-catenin/Tcf signaling: A critical pathway in gastrointestinal tumorigenesis

    Kolligs, F. T.; Bommer, G; Göke, B

    2002-01-01

    Cancers of the gastrointestinal tract, including the liver, bile ducts, and pancreas, constitute the largest group of malignant tumors. Colorectal cancer is one of the most common neoplastic diseases in Western countries and one of the leading causes of cancer-related deaths. Inactivation of the adenomatous polyposis coli (APC) tumor-suppressor gene during early adenoma formation is thought to be the first genetic event in the process of colorectal carcinogenesis followed by mutations in onco...

  1. APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation

    Poulton, John S; Mu, Frank W.; Roberts, David M.; Peifer, Mark

    2013-01-01

    To ensure the accurate transmission of genetic material, chromosome segregation must occur with extremely high fidelity. Segregation errors lead to chromosomal instability (CIN), with deleterious consequences. Mutations in the tumor suppressor adenomatous polyposis coli (APC) initiate most colon cancers and have also been suggested to promote disease progression through increased CIN, but the mechanistic role of APC in preventing CIN remains controversial. Using fly embryos as a model, we inv...

  2. β-Catenin—A Linchpin in Colorectal Carcinogenesis?

    Wong, Newton Alexander Chiang Shuek; Pignatelli, Massimo

    2002-01-01

    An important role for β-catenin pathways in colorectal carcinogenesis was first suggested by the protein’s association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of β-catenin protein expression at all stages of the adenoma-carcinoma sequence. Recent studies have, however, shown that yet more components of colorectal carcinogenesis are linked to β-catenin pathways. Pro-oncogenic factors that also release β-catenin from the adherens complex and/or encourage ...

  3. Funktionelle und molekulare Charakterisierung von Amer3: ein neuer Regulator des Wnt/beta-catenin-Signalwegs

    Brauburger, Katharina

    2013-01-01

    Das Tumorsuppressorprotein APC (adenomatous polyposis coli) ist ein wichtiger negativer Regulator des Wnt/beta-catenin-Signalwegs und spielt im Darm eine entscheidende Rolle in der Proliferation und Differenzierung von Epithelzellen. Mutationen, die zu C-terminal verkürzten APC-Molekülen führen, sind die Hauptursache für die Adenom- und Karzinom-Entwicklung in Darmkrebspatienten. Mit Amer1 und Amer2 wurden zwei Plasmamembran-assoziierte APC-Interaktoren identifiziert, welche di...

  4. HSP105 Recruits Protein Phosphatase 2A To Dephosphorylate β-Catenin

    Yu, Nancy; Kakunda, Michael; Pham, Victoria; Lill, Jennie R.; Du, Pan; Wongchenko, Matthew; Yan, Yibing; Firestein, Ron; Huang, Xiaodong

    2015-01-01

    The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, β-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK3β) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are component...

  5. Self-association of the APC tumor suppressor is required for the assembly, stability, and activity of the Wnt signaling destruction complex

    Kunttas-Tatli, Ezgi; Roberts, David M.; McCartney, Brooke M.

    2014-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling through its activity in the destruction complex with Axin, GSK3β, and CK1 that targets β-catenin/Armadillo (β-cat/Arm) for proteosomal degradation. The destruction complex forms macromolecular particles we termed the destructosome. Whereas APC functions in the complex through its ability to bind both β-cat and Axin, we hypothesize that APC proteins play an additional role in destructosome...

  6. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.

    M. Kitagawa; Hatakeyama, S.; Shirane, M; Matsumoto, M; ISHIDA, N.; K. Hattori; Nakamichi, I; Kikuchi, A; Nakayama, K.

    1999-01-01

    beta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen syntha...

  7. Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers

    Scheel Silvio K; Porzner Marc; Pfeiffer Sabine; Ormanns Steffen; Kirchner Thomas; Jung Andreas

    2010-01-01

    Abstract Background Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (β-CATENIN) gene itself. Recently in Wilms tumo...

  8. Inhibition of WNT Signaling by G Protein-Coupled Receptor (GPCR) Kinase 2 (GRK2)

    WANG, LIMING; Gesty-Palmer, Diane; Fields, Timothy A.; Spurney, Robert F.

    2009-01-01

    Activation of Wnt signaling pathways causes release and stabilization of the transcription regulator β-catenin from a destruction complex composed of axin and the adenomatous polyposis coli (APC) protein (canonical signaling pathway). Assembly of this complex is facilitated by a protein-protein interaction between APC and a regulator of G protein signaling (RGS) domain in axin. Because G protein-coupled receptor kinase 2 (GRK2) has a RGS domain that is closely related to the RGS domain in axi...

  9. Dysregulation of Wnt/β-catenin Signaling in Gastrointestinal Cancers

    White, Bryan D.; Chien, Andy J.; Dawson, David W.

    2011-01-01

    Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal (GI) tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, APC (adenomatous polyposis coli), and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including crosstalk with other altered signaling pathways. A more complex view of Wnt...

  10. Domains of Axin Involved in Protein–Protein Interactions, Wnt Pathway Inhibition, and Intracellular Localization

    Fagotto, François; Jho, Eek-hoon; Zeng, Li; Kurth, Thomas; Joos, Thomas; Kaufmann, Christine; Costantini, Frank

    1999-01-01

    Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3β (GSK3β) and upstream of β-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and β-cat...

  11. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal; Le Grand, Fabien

    2015-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle ste...

  12. El cáncer hereditario en mujeres

    Morales Chamorro, Rafael; Chirivella González, Isabel; Llort Pursals, Gemma; Sánchez Heras, Ana Beatriz; Serrano Blanch, Raquel; Teule Vega, Alexandre; Guillén Ponce, Carmen; Graña Suárez, Begoña

    2015-01-01

    Most cases of cancer are sporadic, whereas 5-10% are hereditary and about 20-30% of cancers tend to cluster in families. Families and individuals who are suspected of suffering from hereditary cancer need to undergo a process known as genetic counseling, which is of considerable importance in the prevention and early detection of malignant tumours. The most common hereditary cancer syndromes are: hereditary breast-ovarian cancer syndrome, familial adenomatous polyposis and Lynch syndrome. Gen...

  13. Cancer Research Repository for Individuals With Cancer Diagnosis and High Risk Individuals.

    2014-12-12

    Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma

  14. Predicting adaptation to presymptomatic DNA testing for late onset disorders: who will experience distress? Rotterdam Leiden Genetics Workgroup.

    DudokdeWit, A C; Tibben, A; Duivenvoorden, H. J.; Niermeijer, M F; Passchier, J

    1998-01-01

    The first comparative study on predicting post-test distress (conceptualised by intrusion and avoidance, measured with the Impact of Event Scale) after presymptomatic genetic testing for Huntington's disease (HD, n=25), cancer syndromes (familial adenomatous polyposis (FAP, n=23)), and hereditary breast and ovarian cancer (HBOC, n=10) is reported. The variables with the highest predictive potential of post-test distress are presented. Participants who were depressed before the test were more ...

  15. Nuclear APC

    Neufeld, Kristi L.

    2009-01-01

    Mutational inactivation of the tumor suppressor gene APC (Adenomatous polyposis coli) is thought to be an initiating step in the progression of the vast majority of colorectal cancers. Attempts to understand APC function have revealed more than a dozen binding partners as well as several subcellular localizations including at cell-cell junctions, associated with microtubules at the leading edge of migrating cells, at the apical membrane, in the cytoplasm and in the nucleus. The present chapte...

  16. Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

    Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D; John L R Rubenstein

    2014-01-01

    Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tan...

  17. Identification of the Modifier of Min 2 (Mom2) Locus, a New Mutation That Influences Apc-Induced Intestinal Neoplasia

    Silverman, Karen A.; Koratkar, Revati; Linda D. Siracusa; Buchberg, Arthur M.

    2002-01-01

    Min (Multiple intestinal neoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al. 1992). Polyp multiplicity in Min mice is greatly influenced by genetic background. A modifier locus, Mom1 (Modifier of Min 1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multipli...

  18. Cystadenocarcinoma of the appendix: an incidental imaging finding in a patient with adenocarcinomas of the ascending and the sigmoid colon

    Prassopoulos Panos

    2003-10-01

    Full Text Available Abstract Background Primary adenocarcinomas of the appendix are uncommon. Mucoceles that result from mucinous adenocarcinomas of the appendix may be incidentally detected on imaging. Case presentation A case of a mucocele of the appendix, due to cystadenocarcinoma, is presented as an incidental imaging finding in a female, 86-year-old patient. The patient was admitted due to rectal hemorrhage and underwent colonoscopy, x-ray, US and CT. Adenocarcinoma of the ascending colon, adenomatous polyp of the sigmoid colon and a cystic lesion in the right iliac fossa were diagnosed. The cystic lesion was characterized as mucocele. The patient underwent right hemicolectomy, excision of the mucocele and sigmoidectomy. She recovered well and in two-year follow-up is free from cancer. Conclusions Preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management, but it is difficult on imaging studies. Small lymph nodes or soft tissue stranding in the surrounding fat on computed tomography examination may suggest the possibility of malignancy.

  19. Comparison between CT Colonography and Double-Contrast Barium Enema for Colonic Evaluation in Patients with Renal Insufficiency

    Chung, Sun Young; Park, Seong Ho; Lee, Seung Soo; Lee, Ju Hee; Kim, Ah Young; Park, Su Ki; Han, Duck Jong; Ha, Hyun Kwon [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    To compare the CT colonography (CTC) and double-contrast barium enema (DCBE) for colonic evaluation in patients with renal insufficiency. Two sequential groups of consecutive patients with renal insufficiency who had a similar risk for colorectal cancer, were examined by DCBE (n = 182; mean {+-} SD in age, 51 {+-} 6.4 years) and CTC (n = 176; 50 {+-} 6.7 years), respectively. CTC was performed after colon cleansing with 250-mL magnesium citrate (n = 87) or 4-L polyethylene glycol (n = 89) and fecal tagging. DCBE was performed after preparation with 250-mL magnesium citrate. Patients with colonic polyps/masses of {>=} 6 mm were subsequently recommended to undergo a colonoscopy. Diagnostic yield and positive predictive value (PPV) for colonic polyps/masses, examination quality, and examination-related serum electrolyte change were retrospectively compared between the two groups. Both the CTC and DCBE were positive for colonic polyps/masses in 28 (16%) of 176 and 11 (6%) of 182 patients, respectively (p = 0.004). Among patients with positive findings, 17 CTC and six DCBE patients subsequently underwent a colonoscopy and yielded a PPV of 88% (15 of 17 patients) and 50% (3 of 6 patients), respectively (p = 0.089). Thirteen patients with adenomatous lesions were detected in the CTC group (adenocarcinoma [n = 1], advanced adenoma [n = 6], and non-advanced adenoma [n = 6]), as compared with two patients (each with adenocarcinoma and advanced adenoma) in the DCBE group (p = 0.003). Six (3%) of 176 CTC and 16 (9%) of 182 DCBE examinations deemed to be inadequate (p 0.046). Electrolyte changes were similar in the two groups. In patients with renal insufficiency, CTC has a higher diagnostic yield and a marginally higher PPV for detecting colorectal neoplasia, despite a similar diagnostic yield for adenocarcinoma, and a lower rate of inadequate examinations as compared with DCBE.

  20. Influenza della presenza di metalli e antiossidanti sullo sviluppo e decorso clinico della poliposi rinosinusale

    Melis, Andrea

    2015-01-01

    Aim: Prevalence of nasal polyposis is about 4%, but its pathogenesis is still unknown. The aim of this work is to evaluate the presence of metals in nasal polyps tissues and to investigate the role of trace elements and antioxidants on nasal polyposis developing and clinic. The metals and antioxidant enzyme levels measured in nasal polyps of 58 patients were compared with the levels measured in nasal biopsies of healthy patients. Methods: 58 adult patients with nasal polyposis and 29 h...

  1. Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome

    Fragulidis Georgios

    2008-10-01

    Full Text Available Abstract Background CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias syndrome has been rarely associated with other malignancies (lung, esophagus.This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. Case presentation A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished food uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative lesion in the third portion of the duodenum was revealed during duodenoscopy, with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and follow-up is negative for local recurrence or metastases 21 months postoperatively. Conclusion CREST syndrome has been associated with colon cancer, gastric polyps, familial adenomatous polyposis (FAP syndrome and Crohn's disease; however, this is the first report of a primary adenocarcinoma of the duodenum in a patient with CREST syndrome. However, any etiologic relationship remains to be further investigated.

  2. Patient - patient interaction

    Birkelund, Regner; Søndergaard Larsen, Lene

    2013-01-01

    occasionally, the opposite was experienced too. Less typically, the patients experienced interaction with fellow patients as a burden and referred to it in negative terms. Conclusions:  Patients’ interaction resembled care as well as self-care. Patient–patient interaction was an important part of the social...... subcategories representing significance of patients’ interaction with fellow patients. Results:  The qualitative analysis resulted in two main categories: (i) Caring for fellow patients and (ii) Sharing illness information with fellow patients. Each of the main categories was elucidated through several...... subcategories. Our findings clearly showed that interpersonal interaction with fellow patients was of utmost importance when it came to care and support and when they needed information about their illness. Typically, the interpersonal interaction was experienced as giving and referred to in positive terms, but...

  3. Clinico-pathological aspects of colorectal serrated adenomas

    Ashish Chandra; Adnan A Sheikh; Anton Cerar; Ian C Talbot

    2006-01-01

    AIM: To study the association of colorectal serrated adenomas (SAs) with invasive carcinoma, local recurrence, synchronicity and metachronicity of lesions.METHODS: A total of 4536 polyps from 1096patients over an eight-year period (1987-1995) were retrospectively examined. Adenomas showing at least 50% of serrated architecture were called SAs by three reviewing pathologists.RESULTS: Ninety-one (2%) of all polyps were called SAs, which were found in 46 patients. Invasive carcinomas were seen in 3 out of 46 (6.4%) patients, of whom one was a case of familial adenomatous polyposis (FAP). A male preponderance was noted and features of a mild degree of dysplasia were seen in majority (n=75,83%) of serrated adenomas. Follow-up ranged 1-12years with a mean time of 5.75 years. Recurrences of SAs were seen in 3 (6.4%) cases, synchronous SAs in 16 (34.8%) cases and metachronous SAs in 9 (19.6%)cases.CONCLUSION: Invasive carcinoma arising in serrated adenoma is rare, accounting for 2 (4.3%) cases studied in this series.

  4. Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients

    Rahul A. Sheth

    2016-01-01

    Full Text Available White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1 the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2 the ability of this system to identify polyps as small as 1 mm, and (3 the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps.

  5. HSP105 recruits protein phosphatase 2A to dephosphorylate β-catenin.

    Yu, Nancy; Kakunda, Michael; Pham, Victoria; Lill, Jennie R; Du, Pan; Wongchenko, Matthew; Yan, Yibing; Firestein, Ron; Huang, XiaoDong

    2015-04-01

    The Wnt/β-catenin pathway causes accumulation of β-catenin in the cytoplasm and its subsequent translocation into the nucleus to initiate the transcription of the target genes. Without Wnt stimulation, β-catenin forms a complex with axin (axis inhibitor), adenomatous polyposis coli (APC), casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK3β) and undergoes phosphorylation-dependent ubiquitination. Phosphatases, such as protein phosphatase 2A (PP2A), interestingly, also are components of this degradation complex; therefore, a balance must be reached between phosphorylation and dephosphorylation. How this balance is regulated is largely unknown. Here we show that a heat shock protein, HSP105, is a previously unidentified component of the β-catenin degradation complex. HSP105 is required for Wnt signaling, since depletion of HSP105 compromises β-catenin accumulation and target gene transcription upon Wnt stimulation. Mechanistically, HSP105 depletion disrupts the integration of PP2A into the β-catenin degradation complex, favoring the hyperphosphorylation and degradation of β-catenin. HSP105 is overexpressed in many types of tumors, correlating with increased nuclear β-catenin protein levels and Wnt target gene upregulation. Furthermore, overexpression of HSP105 is a prognostic biomarker that correlates with poor overall survival in breast cancer patients as well as melanoma patients participating in the BRIM2 clinical study. PMID:25645927

  6. Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

    Takashi Fujimura; Tetsuo Ohta; Katsunobu Oyama; Tomoharu Miyashita; Koichi Miwa

    2006-01-01

    Selective cyclooxygenase (COX)-2 inhibitors (coxibs)were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP),which showed that the treatment with celecoxib,one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinicai use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

  7. Malignant peripheral nerve sheath tumours in inherited disease

    Evans D

    2012-10-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumours (MPNST are rare tumours known to occur at high frequency in neurofibromatosis 1 (NF1, but may also occur in other cancer prone syndromes. Methods The North West Regional Genetic Register covers a population of 4.1 million and was interrogated for incidence of MPNST in 12 cancer prone syndromes. Age, incidence and survival curves were generated for NF1. Results Fifty two of 1254 NF1 patients developed MPNST, with MPNST also occurring in 2/181 cases of schwannomatosis and 2/895 NF2 patients. Three cases were also noted in TP53 mutation carriers. However, there were no cases amongst 5727BRCA1/2 carriers and first degree relatives, 2029 members from Lynch syndrome families, nor amongst 447 Familial Adenomatous Polyposis, 202 Gorlin syndrome, nor 87 vHL cases. Conclusion MPNST is associated with schwannomatosis and TP53 mutations and is confirmed at high frequency in NF1. It appears to be only increased in NF2 amongst those that have been irradiated. The lifetime risk of MPNST in NF1 is between 9–13%.

  8. Composite neuroendocrine and adenomatous carcinoma of the papilla of Vater

    Joanna A Musialik; Maciej J Kohut; Tomasz Marek; Anatol Wodo(I)a(z)ski; Marek Hartleb

    2009-01-01

    Malignant tumors of papilla are usually adenocarcinomas.We present a 67-year-old female who became icteric as result of a malignant tumor infiltrating the papilla of Vater. Histopathological assessment of surgically excised tumor showed both neuroendocrine and adenocarcinomatous features. To our knowledge, this is the seventh report of this rare neoplastic association in the duodenal periampullary region.

  9. Wnt signaling and colon carcinogenesis: Beyond APC

    Rani Najdi

    2011-01-01

    Full Text Available Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical Wnt signaling is modulated by intracellular LEF/TCF composition and location, the action of different Wnt ligands, and the secretion of Wnt inhibitory molecules. We also review the contributions of non-canonical Wnt signaling and other distinct pathways in the tumor micro environment that cross-talk to the canonical Wnt pathway and thereby influence colon cancer progression. These ′non-APC′ aspects of Wnt signaling are considered in relation to the development of potential agents for the treatment of patients with colon cancer. Regulatory pathways that influence Wnt signaling highlight how it might be possible to design therapies that target a network of signals beyond that of APC and β-catenin.

  10. Pathological Diagnosis of Hepatocellular Cellular Adenoma according to the Clinical Context

    Paulette Bioulac-Sage

    2013-01-01

    Full Text Available In Europe and North America, hepatocellular adenomas (HCA occur, classically, in middle-aged woman taking oral contraceptives. Twenty percent of women, however, are not exposed to oral contraceptives; HCA can more rarely occur in men, children, and women over 65 years. HCA have been observed in many pathological conditions such as glycogenosis, familial adenomatous polyposis, MODY3, after male hormone administration, and in vascular diseases. Obesity is frequent particularly in inflammatory HCA. The background liver is often normal, but steatosis is a frequent finding particularly in inflammatory HCA. The diagnosis of HCA is more difficult when the background liver is fibrotic, notably in vascular diseases. HCA can be solitary, or multiple or in great number (adenomatosis. When nodules are multiple, they are usually of the same subtype. HNF1α-inactivated HCA occur almost exclusively in woman. The most important point of the classification is the identification of β-catenin mutated HCA, a strong argument to identify patients at risk of malignant transformation. Some HCA already present criteria indicating malignant transformation. When the whole nodule is a hepatocellular carcinoma, it is extremely difficult to prove that it is the consequence of a former HCA. It is occasionally difficult to identify HCA remodeled by necrosis or hemorrhage.

  11. Aberrant WNT/β-catenin signaling in parathyroid carcinoma

    Åkerström Göran

    2010-11-01

    Full Text Available Abstract Background Parathyroid carcinoma (PC is a very rare malignancy with a high tendency to recur locally, and recurrent disease is difficult to eradicate. In most western European countries and United States, these malignant neoplasms cause less than 1% of the cases with primary hyperparathyroidism, whereas incidence as high as 5% have been reported from Italy, Japan, and India. The molecular etiology of PC is poorly understood. Results The APC (adenomatous polyposis coli tumor suppressor gene was inactivated by DNA methylation in five analyzed PCs, as determined by RT-PCR, Western blotting, and quantitative bisulfite pyrosequencing analyses. This was accompanied by accumulation of stabilized active nonphosphorylated β-catenin, strongly suggesting aberrant activation of the WNT/β-catenin signaling pathway in these tumors. Treatment of a primary PC cell culture with the DNA hypomethylating agent 5-aza-2'-deoxycytidine (decitabine, Dacogen(r induced APC expression, reduced active nonphosphorylated β-catenin, inhibited cell growth, and caused apoptosis. Conclusion Aberrant WNT/β-catenin signaling by lost expression and DNA methylation of APC, and accumulation of active nonphosphorylated β-catenin was observed in the analyzed PCs. We suggest that adjuvant epigenetic therapy should be considered as an additional option in the treatment of patients with recurrent or metastatic parathyroid carcinoma.

  12. Effect of Eicosapentaenoic Acid on E-type Prostaglandin Synthesis and EP4 Receptor Signaling Human Colorectal Cancer Cells

    Gillian Hawcroft

    2010-08-01

    Full Text Available The ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA, in the free fatty acid (FFA form, has been demonstrated to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPAFFA negatively modulates synthesis of and signaling by prostaglandin (PG E2 in human colorectal cancer (CRC cells. EPA-FFA induced apoptosis of cyclooxygenase (COX-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as a substrate for COX-2, leading to reduced synthesis of PGE2 and generation of PGE3. Alone, PGE3 bound and activated the PGE2 EP4 receptor but with reduced affinity and efficacy compared with its “natural” ligand PGE2. However, in the presence of PGE2, PGE3 acted as an antagonist of EP4 receptor-dependent 3’,5’ cyclic adenosine monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2dependent “PGE2-to-PGE3 switch” in human CRC cells and that PGE3 acts as a partial agonistat the PGE2 EP4 receptor.

  13. Thyroid abnormality trend over time in northeastern regions of Kazakstan, adjacent to the Semipalatinsk nuclear test site. A case review of pathological findings for 7271 patients

    From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population. (author)

  14. Frequency of endometrial carcinoma in patients with postmenopausal bleeding

    Introduction: Postmenopausal bleeding (PMB) is defined as bleeding that occurs after 1 year of amenorrhea in a woman who is not receiving hormone replacement therapy (HRT). About 10% of women with postmenopausal bleeding have a primary or secondary malignancy. Common malignancies among them are endometrial cancer (80%), cervical cancer or an ovarian tumour. Endometrial cancer is the second most common cancer associated with hereditary non-polyposis colorectal cancer. Ninety percent of patients have benign causes. Objective: The objective of this study was to determine the frequency of endometrial carcinoma in patients with post-menopausal bleeding. Study Design: Descriptive case series study. Setting: Department of obstetrics and gynaecology, Lady Willingdon, Lahore. Duration of Study: This study was conducted over a period of six months from January, 1 2009 to June 30, 2009. Subjects and Methods: 50 cases with postmenopausal bleeding. Results: During the period of this study a total number of 50 consecutive patients who met inclusion criteria were enrolled in the study. Ages of the patients who presented with PMB ranged between 48 years and 80 years with a mean age of 59 years. Malignancy was found in 18 out of 50 cases (36%).Cases with endometrial CA were 14 out of 50 cases (28%) and CA cervix constituted 4 out of 50 cases (8%). Benign pathology was more frequent (64%). 13 of 50 cases (26%) had hyperplasia out of which 1 case (2%) was of atypical hyperplasia. Endometrial polyp was found in 4 of 50 cases (8%). 3 of 50 cases (6%) had chronic endometritis. 5 of 50 cases (10%) had chronic cervicitis. While 7 cases (14%) had postmenopausal bleeding due to decubitus ulcer of uterovaginal prolapse. Among malignancies (36%), endometrial cancer is the most frequent malignancy in women with postmenopausal bleeding with mean age of 65 years. Conclusion: In this study it was concluded that the majority of cases of PMB would be expected to be suffering from benign problems

  15. Patient satisfaction

    Bhanu Prakash

    2010-01-01

    Full Text Available Patient satisfaction is an important and commonly used indicator for measuring the quality in health care. Patient satisfaction affects clinical outcomes, patient retention, and medical malpractice claims. It affects the timely, efficient, and patient-centered delivery of quality health care. Patient satisfaction is thus a proxy but a very effective indicator to measure the success of doctors and hospitals. This article discusses as to how to ensure patient satisfaction in dermatological practice.

  16. Clinical significance of blood lipid、lipoprotein、chemerin and fecal calprotectin determination in patients with colorectal adenomatous%结直肠腺瘤患者血脂、脂蛋白、脂肪因子及粪钙卫蛋白水平检测的临床意义

    杨卫文; 黎莉; 谭松; 魏涛; 刘正勇

    2012-01-01

    ①目的 探讨检测结直肠腺瘤患者血脂、脂蛋白、脂肪因子(chemerin)及粪钙卫蛋白水平的临床意义.②方法 选取结直肠腺瘤患者168例,健康对照组52例,收集清晨静脉血及一次大便标本,分别测定血清TC、TG、HDL-C、LDL-C、chemerin及粪钙卫蛋白水平,并根据腺瘤的部位、大小、组织成分、瘤变的情况进行分组,分别比较各组的测定值.腺瘤摘除后3、6月及1年作肠镜随访,同时测定上述各指标.③结果 腺瘤组血TC、TG、LDL-C、chemerin及粪钙卫蛋白水平较对照组显著升高(P<0.01及0.05),HDL-C水平显著下降(P<0.05).腺瘤各亚组测定值也有相应改变,腺瘤摘除后3月开始血TC、TG、LDL-C,chemerin及粪钙卫蛋白水平显著下降,HDL-C水平显著升高,摘除后6月及1年复发患者血TC、TG、LDL-C、chemerin及粪钙卫蛋白水平较未复发患者显著升高,HDL-C水平显著下降,达摘除前水平.相关分析表明,TC、TG、LDL-C与chemerin粪钙卫蛋白水平呈正相关,HDL-C与之呈负相关,血chemerin与粪钙卫蛋白水平也呈正相关.④结论 血TC、TG、LDL-C、chemerin及粪钙蛋白与腺瘤的发生、发展及恶变有关,HDL-C对其有抑制作用,监测血TC、TG、HDL-C、LDL-C chemerin及粪钙蛋白水平可以帮助了解腺瘤复发情况.

  17. High prevalence of germline STK11 mutations in Hungarian Peutz-Jeghers Syndrome patients

    Kasler Miklos

    2010-11-01

    Full Text Available Abstract Background Peutz-Jeghers syndrome (PJS is a rare autosomal dominantly inherited disease characterized by gastrointestinal hamartomatous polyposis and mucocutaneous pigmentation. The genetic predisposition for PJS has been shown to be associated with germline mutations in the STK11/LKB1 tumor suppressor gene. The aim of the present study was to characterize Hungarian PJS patients with respect to germline mutation in STK11/LKB1 and their association to disease phenotype. Methods Mutation screening of 21 patients from 13 PJS families were performed using direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA. Comparative semi-quantitative sequencing was applied to investigate the mRNA-level effects of nonsense and splice-affecting mutations. Results Thirteen different pathogenic mutations in STK11, including a high frequency of large genomic deletions (38%, 5/13, were identified in the 13 unrelated families studied. One of these deletions also affects two neighboring genes (SBNO2 and GPX4, located upstream of STK11, with a possible modifier effect. The majority of the point mutations (88%, 7/8 can be considered novel. Quantification of the STK11 transcript at the mRNA-level revealed that the expression of alleles carrying a nonsense or frameshift mutation was reduced to 30-70% of that of the wild type allele. Mutations affecting splice-sites around exon 2 displayed an mRNA processing pattern indicative of co-regulated splicing of exons 2 and 3. Conclusions A combination of sensitive techniques may assure a high (100% STK11 mutation detection frequency in PJS families. Characterization of mutations at mRNA level may give a deeper insight into the molecular consequences of the pathogenic mutations than predictions made solely at the genomic level.

  18. Filiform polyposis in a child with Crohn's disease

    Filiform polyps were demonstrated radiographically in a seven year old child with granulomatous colitis. Most previous reports have been in adult subjects. These slender projections of colonic mucosa and submucosa have a characteristic radiographic appearance on barium enema. It is important to recognize the condition as being benign. (orig.)

  19. AXIN1 and AXIN2 variants in gastrointestinal cancers.

    Mazzoni, Serina M; Fearon, Eric R

    2014-12-01

    Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and AXIN1/2 alterations have been proposed as key defects in some cancers. Here, we review AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development. PMID:25236910

  20. Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice

    Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja; van Kranen, H.; van Kreijl, C.; Fodde, R.; Thorgeirsson, S. S.

    1997-01-01

    Transgenic Apc1638N mice, heterozygous for a targeted frameshift mutation at codon 1638 of the endogenous adenomatous polyposis coli (APC) gene, are predisposed to develop multiple adenomas and adenocarcinomas along the intestinal tract and to a number of extra-intestinal lesions including, among...... increased number of small intestinal tumors as well as an increased number of aberrant crypt foci (ACF) were observed in male Apc(+)/Apc1638N mice compared with untreated transgenic mice, No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc(+)/Apc1638N...

  1. Clinical significance of detection of human telomerase reverse transcriptase in colorectal cancer and its precancerous lesions

    刘少平

    2014-01-01

    Objective To evaluate the expression and clinical significance of human telomerase reverse transcriptase(h TERT)in colorectal cancer and its precancerous lesion.Methods The levels of h TERT expression were detected by immunohistochemistry in colorectal cancers(n=95),colorectal adenomatous polyposis(n=30)and normal colorectal tissues(n=30).The relationship between the expression of h TERT in colorectal cancer tissues and the pathologic features and prognosis were analyzed.Results The positive rate of h TERT expression

  2. Crystal structure of a β-catenin/Axin complex suggests a mechanism for the β-catenin destruction complex

    Xing, Yi; Clements, Wilson K.; Kimelman, David; Xu, Wenqing

    2003-01-01

    The “β-catenin destruction complex” is central to canonical Wnt/β-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid β-catenin turnover. We determined the crystal structure of a complex between β-catenin and the β-catenin-binding domain of Axin (Axin-CBD). The Axin-CBD forms a helix that occupies the groove formed by the third and fourth armadillo repeats of β-catenin and...

  3. A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression

    Zeineldin, Maged; Cunningham, Jamie; McGuinness, William; Alltizer, Preston; Cowley, Brett; Blanchat, Bryan; Xu, Wenhao; Pinson, David; Neufeld, Kristi L.

    2011-01-01

    Mutation of the tumor suppressor adenomatous polyposis coli (APC) is considered an initiating step in the genesis of the vast majority of colorectal cancers. APC inhibits the Wnt signaling pathway by targeting proto-oncogene β-catenin for destruction by cytoplasmic proteasomes. In the presence of a Wnt signal, or in the absence of functional APC, β-catenin can serve as a transcription co-factor for genes required for cell proliferation such as cyclin D1 and c-Myc. In cultured cells, APC shutt...

  4. Frequent loss of the AXIN1 locus but absence of AXIN1 gene mutations in adenocarcinomas of the gastro-oesophageal junction with nuclear β-catenin expression

    Koppert, L.B.; Velden, A.W. van der; Van de Wetering, M; Abbou, M.; van den Ouweland, A M W; Tilanus, H W; Wijnhoven, B P L; Dinjens, W.N.M.

    2004-01-01

    Up to 60% of gastro-oesophageal junction (GEJ) adenocarcinomas show nuclear β-catenin expression, pointing to activated T-cell factor (TCF)/β-catenin-driven gene transcription. We demonstrate in five human GEJ adenocarcinoma cell lines that nuclear β-catenin expression indeed correlates with enhanced TCF-mediated transcription of a reporter gene. In several tumour types, TCF/β-catenin activation is caused by mutations in either adenomatous polyposis coli (APC), β-catenin exon 3, AXIN1, AXIN2 ...

  5. The β-Catenin Destruction Complex

    Stamos, Jennifer L.; Weis, William I.

    2013-01-01

    The Wnt/β-catenin pathway is highly regulated to insure the correct temporal and spatial activation of its target genes. In the absence of a Wnt stimulus, the transcriptional coactivator β-catenin is degraded by a multiprotein “destruction complex” that includes the tumor suppressors Axin and adenomatous polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase β-TrCP. The complex generates a β-TrCP recognition site by phosphorylation ...

  6. Physiological regulation of β-catenin stability by Tcf3 and CK1ε

    Lee, Ethan; Salic, Adrian; Kirschner, Marc W.

    2001-01-01

    The wnt pathway regulates the steady state level of β-catenin, a transcriptional coactivator for the Tcf3/Lef1 family of DNA binding proteins. We demonstrate that Tcf3 can inhibit β-catenin turnover via its competition with axin and adenomatous polyposis for β-catenin binding. A mutant of β-catenin that cannot bind Tcf3 is degraded faster than the wild-type protein in Xenopus embryos and extracts. A fragment of β-catenin and a peptide encoding the NH2 terminus of Tcf4 that block the interacti...

  7. Helicobacter hepaticus Infection Promotes Colon Tumorigenesis in the BALB/c-Rag2−/− ApcMin/+ Mouse ▿

    Nagamine, Claude M; Sohn, Jane J.; Rickman, Barry H.; Rogers, Arlin B.; Fox, James G.; Schauer, David B.

    2008-01-01

    Adenomatous polyposis coli (APC) mutations are linked to human and mouse colorectal cancers. The Apc multiple intestinal neoplasia (Min) mouse mutation causes adenomas to develop throughout the small and large intestines. The BALB-Min (C.B6-ApcMin/+) congenic strain was generated by backcrossing into BALB/c the ApcMin allele from C57BL/6J-ApcMin/+ mice. BALB-Min mice have a low tumor multiplicity (27.4 small intestine tumors/mouse) and a relatively long life span (>1 year) that makes them ame...

  8. Usefulness of fine-needle aspiration in the diagnosis of thyroid lesions: an institutional experience of 340 patients

    Pinki Pandey

    2013-12-01

    Full Text Available Objective: To evaluate the results of fine needle aspiration cytology (FNAC in the diagnosis, its correlation with histology, to highlight its limitations and diagnostic pitfalls as well as the impact of FNAC on the decreased rate of surgery in clinically suspect thyroid lesions.Study design: FNAC was performed on 340 patients with thyroid enlargement over a period of six years. The cytological results were correlated with clinical features, thyroid function tests and histopathological examination.Results: Among non- neoplastic group, the most frequently encountered lesion was colloid goiter in 231 (67.94% cases followed by thyroiditis in 68 (20% cases, five (1.47% adenomatous goiter and four (1.17% thyroglossal cysts. Among the neoplasticgroup, twelve (3.52% cases were reported as follicular neoplasm, seven (2.05% cases as Hürthle cell neoplasm and four (1.17% as malignant tumors. The cytological and histological concordance was determined. A false positive cytologic diagnosis of neoplasms was made in five cases. Presence of Hürthle cell metaplasia, hyperplastic nodules and papillary hyperplasia were responsible for the false positive diagnoses. For the entire series, the false negative rate was 8.57% and the false positive rate was 7.14%. FNA revealed a sensitivity of 62.5%, a specificity of 90.74%, a positive predictive value of 66.66% and a negative predictive value of 89.09%.Conclusion: FNAC is thus an accurate, cost- effective, minimally invasive and reliable diagnostic tool for assessment of patients with thyroid lesions and their management.

  9. Intraepithelial lymphocytosis is a frequent finding in biopsies from ileal pouch-anal anastomoses.

    Schaeffer, David F; Walsh, Joanna C; Tyler, Andrea D; Ben-Bassat, Ofer; Silverberg, Mark S; Riddell, Robert H; Kirsch, Richard

    2016-08-01

    Following restorative proctocolectomy with an ileal pouch-anal anastomosis, the small bowel mucosa undergoes several specific histologic adaptions, which may be unrelated to the underlying disease or symptoms of pouchitis. An increase in intraepithelial lymphocytes (IELs) has not been described as part of this spectrum. Mucosal biopsies of the ileal pouch and afferent limb of 230 patients (mean age: 45.7y [18.3-74.7], gender [female/male]: 117/113) with a functioning ileal pouch-anal anastomosis (mean time since ileostomy closure: 10.8months) and associated clinically annotated outcome data were assessed for IELs/100 enterocytes. Forty-two patients (18.3%) showed an increase in IELs (≥20 IELs/100 enterocytes [range 20-39]), in pouch and/or afferent limb biopsies. Intraepithelial lymphocytosis was more commonly observed in afferent limb compared to pouch biopsies (18.8% vs 8.3%; P = .42) and in familial adenomatous polyposis compared to ulcerative colitis patients (16% vs 8%; P = 0.36), but neither difference reached statistical significance. No cases with increased IELs displayed severe villous blunting. Increased IELs were not significantly associated with age, sex, ethnicity, smoking history, time since ileostomy, use of antibiotics, biologic agents, anti-diarrheal agents or probiotics, C-reactive protein levels or differential white cell count. None of the 42 patients with increased IELs had positive celiac serology (anti-human tissue transglutaminase IgA [ELISA] with corresponding total serum IgA). Intraepithelial lymphocytosis in pouch biopsies may represent a subclinical response to an altered bacterial microenvironment. Pathologists should be aware that intraepithelial lymphocytosis is part of the spectrum of changes in pouch biopsies, and only rarely is due to celiac disease. PMID:27063473

  10. A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

    Smith, F M

    2012-02-03

    INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict\\/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

  11. Patient life

    Ludvigsen, Mette Spliid

    2004-01-01

    Background: The hypothesis for the study is that the informal relationships amongst patients during hospitalisation have more influence on wellbeing, understanding of own illnesses and recovery than we until now have recognised in nursing. Aim: The purpose is to describe patients' experiences of ...

  12. Discharging patients.

    Causey, Amy

    2016-06-22

    What was the nature of the CPD activity and/or practice-related feedback and/or event or experience in your practice? The CPD article discussed the importance of effective planning when discharging patients from acute care hospitals. It emphasised the benefit of early assessment and planning, and outlined the essential principles that should be followed when discharging a patient. PMID:27332612

  13. Patient education.

    Lindeman, C A

    1988-01-01

    The 120 studies included in this review were grouped in relation to five categories of variables basic to a theory of instruction in patient education. Findings in the studies related to the characteristics of the patient as learner support the following variables as significant for a theory of instruction: demographic characteristics including age, race, duration and type of illness, educational level, and family preparedness. Selected psychological variables are significant as they interact with teaching approaches. Given only two studies in which the characteristics of the nurse as teacher were the main variables, no inferences for a theory of instruction could be drawn. However, the findings from those studies combined with results from studies in which characteristics of the nurse were secondary variables support the importance of this category of variables. The educational preparation, motivation, values, and job description of the nurse implementing patient teaching appear to be significant variables for a theory of instruction. Investigators explored a wide range of teaching strategies in the studies of patient teaching. The setting for teaching, group and individual teaching, and a variety of instructional strategies all prove promising at the operational level. The instructional strategies were too diverse to allow analysis at a level of abstraction beyond the operational. Findings in this review also support characteristics of the health care setting as an important category of variables for a theory of instruction. The organizational structure, a quality assurance framework, and valuing patient teaching appear to be significant variables. Patient education research provides a rich data source for future developments in theory, practice, and research. The effectiveness of patient education as a nursing intervention is clearly established. Furthermore, positive learning outcomes are associated with a broad range of teaching strategies, content areas, and

  14. Uso de analgésicos e antiinflamatórios em pacientes portadores de polipose nasossinusal eosinofílica tolerantes e intolerantes à aspirina Use of analgesics and anti-inflammatory drugs in patients with eosinophilic nasal polyposis tolerant and intolerant to aspirin

    Helena M. G. Becker; Evaldo Nascimento; Roberto E. S. Guimarães; Celso G. Becker; Paulo F. T. B. Crosara; Wanessa D. de Oliveira

    2003-01-01

    Com a introdução da aspirina como medicamento foram descritos diversos relatos de reações adversas. A associação de intolerância aspirínica (IA), polipose nasal (PNS) e asma foi inicialmente observada por Widals et al.(1922)¹, e posteriormente Samter & Beers (1967)². Esta intolerância se manifesta principalmente por obstrução nasal e/ou broncoespasmo, decorrente da inibição da ciclooxigenase-1 (COX-1) e conseqüente aumento de leucotrienos (LT). A intolerância também ocorre após a ingestão de ...

  15. Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.

    Gavert, Nancy; Yaron, Yuval; Naiman, Tova; Bercovich, Dani; Rozen, Paul; Shomrat, Ruth; Legum, Cyril; Orr-Urtreger, Avi

    2002-06-01

    Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP. PMID:12007223

  16. Cronkhite-Canada syndrome associated with rib fractures: a case report

    Wan Haijun

    2010-10-01

    Full Text Available Abstract Background Cronkhite-Canada syndrome (CCS is a rare multiple gastrointestinal polyposis. Up till now, many complications of CCS have been reported in the literature, but rib fracture is not included. Case Presentation We report a case of a 58-year-old man who was admitted to our hospital with a 6-month history of frequent diarrhea, intermittent hematochezia and a weight loss of 13 kg. On admission, physical examination revealed alopecia of the scalp, hyperpigmentation of the hands and soles, and dystrophy of the fingernails. Laboratory data revealed hypocalcaemia and hypoproteinemia. Esophagogastroduodenoscopy, video capsule endoscopy and colonoscopy revealed various sizes of generalized gastrointestinal polyps. Histological examination of the biopsy specimens obtained from the stomach and the colon showed adenomatous polyp and inflammatory polyp respectively. Thus, a diagnosis of CCS was made. After treatment with corticosteroids for 24 days and nutritional support for two months, his clinical condition improved. Two months later, he was admitted to our hospital for the second time with frequent diarrhea and weight loss. The chest radiography revealed fractures of the left sixth and seventh ribs. Examinations, including emission computed tomography, bone densitometry test, and other serum parameters, were performed, but could not identify the definite etiology of the rib fractures. One month later, the patient suffered from aggravating multiple rib fractures due to the ineffective treatment, persistent hypocalcaemia and malnutrition. Conclusions This is the first case of a CCS patient with multiple rib fractures. Although the association between CCS and multiple rib fractures in this case remains uncertain, we presume that persistent hypocalcaemia and malnutrition contribute to this situation, or at least aggravate this rare complication. Besides, since prolonged corticosteroid therapy will result in an increased risk of osteoporotic

  17. chemotherapy patients

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  18. Differential gene expression profile reveals deregulation of pregnancy specific β1 glycoprotein 9 early during colorectal carcinogenesis

    Gallinger Steven

    2005-06-01

    Full Text Available Abstract Background APC (Adenomatous polyposis coli plays an important role in the pathogenesis of both familial and sporadic colorectal cancer. Patients carrying germline APC mutations develop multiple colonic adenomas at younger age and higher frequency than non-carrier cases which indicates that silencing of one APC allele may be sufficient to initiate the transformation process. Methods To elucidate the biological dysregulation underlying adenoma formation we examined global gene expression profiles of adenomas and corresponding normal mucosa from an FAP patient. Differential expression of the most significant gene identified in this study was further validated by mRNA in situ hybridization, reverse transcriptase PCR and Northern blotting in different sets of adenomas, tumours and cancer cell lines. Results Eighty four genes were differentially expressed between all adenomas and corresponding normal mucosa, while only seven genes showed differential expression within the adenomas. The first group included pregnancy specific β-1 glycoprotein 9 (PSG9 (p PSG9 is a member of the carcinoembryonic antigen (CEA/PSG family and is produced at high levels during pregnancy, mainly by syncytiotrophoblasts. Further analysis of sporadic and familial colorectal cancer confirmed that PSG9 is ectopically upregulated in vivo by cancer cells. In total, deregulation of PSG9 mRNA was detected in 78% (14/18 of FAP adenomas and 75% (45/60 of sporadic colorectal cancer cases tested. Conclusion Detection of PSG9 expression in adenomas, and at higher levels in FAP cases, indicates that germline APC mutations and defects in Wnt signalling modulate PSG9 expression. Since PSG9 is not found in the non-pregnant adult except in association with cancer, and it appears to be an early molecular event associated with colorectal cancer monitoring of its expression may be useful as a biomarker for the early detection of this disease.

  19. Genomic Landscape of Colorectal Mucosa and Adenomas.

    Borras, Ester; San Lucas, F Anthony; Chang, Kyle; Zhou, Ruoji; Masand, Gita; Fowler, Jerry; Mork, Maureen E; You, Y Nancy; Taggart, Melissa W; McAllister, Florencia; Jones, David A; Davies, Gareth E; Edelmann, Winfried; Ehli, Erik A; Lynch, Patrick M; Hawk, Ernest T; Capella, Gabriel; Scheet, Paul; Vilar, Eduardo

    2016-06-01

    The molecular basis of the adenoma-to-carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances (AI) in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. Cancer Prev Res; 9(6); 417-27. ©2016 AACR. PMID:27221540

  20. Diagnosis and Management of Hereditary Thyroid Cancer.

    Bano, Gul; Hodgson, Shirley

    2016-01-01

    Thyroid cancers are largely divided into medullary (MTC) and non-medullary (NMTC) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5-15% of NMTC and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden's disease , Werner's syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20-25% of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the RET oncogene on chromosome 10q11.2. There is a clear genotype-phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery. PMID:27075347

  1. Colonic polyps: inheritance, susceptibility, risk evaluation, and diagnostic management

    Colorectal cancer (CRC) is the third-ranked neoplasm in order of incidence and mortality, worldwide, and the second cause of cancer death in industrialized countries. One of the most important environmental risk factors for CRC is a Western-type diet, which is characterized by a low-fiber and high-fat content. Up to 25% of patients with CRC have a family history for CRC, and a fraction of these patients are affected by hereditary syndromes, such as familial adenomatous polyposis, Gardner or Turcot syndromes, or hereditary nonpolyposis colorectal cancer. The onset of CRC is triggered by a well-defined combination of genetic alterations, which form the bases of the adenoma-carcinoma sequence hypothesis and justify the set-up of CRC screening techniques. Several screening and diagnostic tests for CRC are illustrated, including rectosigmoidoscopy, optical colonoscopy (OC), double contrast barium enema (DCBE), and computed tomography colonography (CTC). The strengths and weaknesses of each technique are discussed. Particular attention is paid to CTC, which has evolved from an experimental technique to an accurate and mature diagnostic approach, and gained wide acceptance and clinical validation for CRC screening. This success of CTC is due mainly to its ability to provide cross-sectional analytical images of the entire colon and secondarily detect extracolonic findings, with minimal invasiveness and lower cost than OC, and with greater detail and diagnostic accuracy than DCBE. Moreover, especially with the advent and widespread availability of modern multidetector CT scanners, excellent quality 2D and 3D reconstructions of the large bowel can be obtained routinely with a relatively low radiation dose. Computer-aided detection systems have also been developed to assist radiologists in reading CTC examinations, improving overall diagnostic accuracy and potentially speeding up the clinical workflow of CTC image interpretation

  2. Knowing Patients

    Pflueger, Dane

    2016-01-01

    accounting for the views of consumers and of holding providers accountable for their care. These movements are shown to entail the staging and stabilizing of “knowing patients” in both senses of the term: these are patients that are equipped and empowered as consumers with knowledge about quality and their...

  3. Patient Roadmap

    ... do anything to deserve this. Find ways to increase relaxation. Patients often report that their tinnitus is less burdensome when they are relaxed. Find the activities and behaviors that best help you relax: exercise, yoga, meditation, soothing music, anything that helps you ...

  4. Patient Empowerment

    ... A Patient’s Perspective Live Living With Kidney Cancer Cancer Nutrition Information (AICR) Emotional Well-Being Patient Empowerment Support ... want to help themselves. Vitamin supplements and good nutrition have a role to play in cancer care. However, large doses of some supplements may ...

  5. Refugee patients.

    Valeras, Aimee Burke

    2016-06-01

    This short story focuses on refugee patients. Family members talk about the horrific struggles of civil war, refugee camps, and promises of US resettlement. Their harsh reception into a brutal world includes unemployment, food scarcity, and isolation. (PsycINFO Database Record PMID:27270253

  6. Structural and functional characterization of the Wnt inhibitor APC membrane recruitment 1 (Amer1).

    Tanneberger, Kristina; Pfister, Astrid S; Kriz, Vitezslav; Bryja, Vitezslav; Schambony, Alexandra; Behrens, Jürgen

    2011-06-01

    Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing β-catenin degradation. We show here that Amer1 directly interacts with the armadillo repeats of β-catenin via a domain consisting of repeated arginine-glutamic acid-alanine (REA) motifs, and that Amer1 assembles the β-catenin destruction complex at the plasma membrane by recruiting β-catenin, adenomatous polyposis coli, and Axin/Conductin. Deletion or specific mutations of the membrane binding domain of Amer1 abolish its membrane localization and abrogate negative control of Wnt signaling, which can be restored by artificial targeting of Amer1 to the plasma membrane. In line, a natural splice variant of Amer1 lacking the plasma membrane localization domain is deficient for Wnt inhibition. Knockdown of Amer1 leads to the activation of Wnt target genes, preferentially in dense compared with sparse cell cultures, suggesting that Amer1 function is regulated by cell contacts. Amer1 stabilizes Axin and counteracts Wnt-induced degradation of Axin, which requires membrane localization of Amer1. The data suggest that Amer1 exerts its negative regulatory role in Wnt signaling by acting as a scaffold protein for the β-catenin destruction complex and promoting stabilization of Axin at the plasma membrane. PMID:21498506

  7. A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia.

    Rivera, B; Perea, J; Sánchez, E; Villapún, M; Sánchez-Tomé, E; Mercadillo, F; Robledo, M; Benítez, J; Urioste, M

    2014-03-01

    Truncating mutations in the AXIN2 gene, a key regulator of β-catenin degradation in the Wnt pathway, have been reported in three families with gastrointestinal adenomatous polyposis and features of ectodermal dysplasia. However, the role of AXIN2 in familial adenomatous polyposis (FAP) syndrome is not completely understood. We performed an in-depth study of APC and MUTYH, and ruled out their implication in 23 FAP families. We then investigated the role of other genes involved in the Wnt pathway, including AXIN2, and identified a novel missense variant in AXIN2 in one family with attenuated FAP. Carriers of the variant exhibited a variable number of polyps but none showed any sign of ectodermal dysplasia. We have demonstrated the pathogenicity of this novel variant by establishing its low frequency in controls as well as by LOH analysis, a segregation study, and immunofluorescent staining of AXIN2 and β-catenin proteins. This report expands the phenotype known to be related to AXIN2 alterations and raises the question of whether to screen AXIN2 in FAP cases negative for alterations in APC and MUTYH. PMID:23838596

  8. Targeting Stem Cell Behavior in Desmoid Tumors (Aggressive Fibromatosis by Inhibiting Hedgehog Signaling

    Ronak Ghanbari-Azarnier

    2013-07-01

    Full Text Available Desmoid tumor (also called aggressive fibromatosis is a lesion of mesenchymal origin that can occur as a sporadic tumor or a manifestation of the preneoplastic syndrome, familial adenomatous polyposis caused by a mutation in adenomatous polyposis coli (APC. This tumor type is characterized by the stabilization of β-catenin and activation of Tcf-mediated transcription. Cell transplantation data suggest that desmoid tumors are derived from mesenchymal progenitor cells (MSCs. As such, modulating cell signaling pathways that regulate MSC differentiation or proliferation, such as hedgehog (Hh signaling, could alter the tumor phenotype. Here, we found that Hh signaling is activated in human and murine desmoid tumors. Inhibiting Hh signaling in human cell cultures decreased cell proliferation and β-catenin protein levels. Apc+/Apc1638N mice, which develop desmoid tumors, develop smaller and fewer tumors when Hh signaling was inhibited either genetically (by crossing Apc+/Apc1638N mice with mice lacking one copy of a Hh-activated transcription factor, Gli2+/-mice or using a pharmacologic inhibitor. Both in mice and in human tumor cell cultures, β-catenin and Hh-mediated signaling positively regulate each other's activity. These data show that targeting a pathway that regulates MSC differentiation influences desmoid tumor behavior, providing functional evidence supporting the notion that these tumors are derived from mesenchymal progenitors. It also suggests Hh blockade as a therapeutic approach for this tumor type.

  9. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  10. Genetic mechanisms in Apc-mediated mammary tumorigenesis.

    Mari Kuraguchi

    2009-02-01

    Full Text Available Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC.

  11. The insulin receptor substrate 1 (IRS1 in intestinal epithelial differentiation and in colorectal cancer.

    Diana L Esposito

    Full Text Available Colorectal cancer (CRC is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1 is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining intensity was significantly higher in metastases relative to both primary CRC (P<0.01 and colonic epithelium (P<0.01. Primary and metastatic CRCs, compared to colonic epithelium, contained significantly higher numbers of IRS1-positive cells (P = 0.013 and P = 0.014, respectively. Pathologic correlations in 163 primary CRCs revealed that diffuse IRS1 staining was associated with tumors combining differentiated phenotype and aggressive markers (high Ki67, p53, and ß-catenin. In Caco 2 IRS1 and InsR were maximally expressed after polarization, while IGF1R was highest in pre-polarized cells. No nuclear IRS1 was detected, while, with polarization, phosphorylated IRS1 (pIRS1 shifted from the lateral to the apical plasma membrane and was expressed in surface cells only. In HT29, that carry mutations constitutively activating survival signaling, IRS1 and IGF1R decreased with polarization, while pIRS1 localized in nuclear spots throughout the course. Overall, these data provide evidence that IRS1 is modulated according to CRC differentiation, and support a role of IRS1 in CRC progression and liver metastatization.

  12. The insulin receptor substrate 1 (IRS1) in intestinal epithelial differentiation and in colorectal cancer.

    Esposito, Diana L; Aru, Federica; Lattanzio, Rossano; Morgano, Annalisa; Abbondanza, Michela; Malekzadeh, Reza; Bishehsari, Faraz; Valanzano, Rosa; Russo, Antonio; Piantelli, Mauro; Moschetta, Antonio; Lotti, Lavinia Vittoria; Mariani-Costantini, Renato

    2012-01-01

    Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining intensity was significantly higher in metastases relative to both primary CRC (P<0.01) and colonic epithelium (P<0.01). Primary and metastatic CRCs, compared to colonic epithelium, contained significantly higher numbers of IRS1-positive cells (P = 0.013 and P = 0.014, respectively). Pathologic correlations in 163 primary CRCs revealed that diffuse IRS1 staining was associated with tumors combining differentiated phenotype and aggressive markers (high Ki67, p53, and ß-catenin). In Caco 2 IRS1 and InsR were maximally expressed after polarization, while IGF1R was highest in pre-polarized cells. No nuclear IRS1 was detected, while, with polarization, phosphorylated IRS1 (pIRS1) shifted from the lateral to the apical plasma membrane and was expressed in surface cells only. In HT29, that carry mutations constitutively activating survival signaling, IRS1 and IGF1R decreased with polarization, while pIRS1 localized in nuclear spots throughout the course. Overall, these data provide evidence that IRS1 is modulated according to CRC differentiation, and support a role of IRS1 in CRC progression and liver metastatization. PMID:22558377

  13. Photoprotective effects of sulindac against ultraviolet B-induced phototoxicity in the skin of SKH-1 hairless mice

    Sulindac is a nonsteroidal anti-inflammatory drug with demonstrated potency as a chemopreventive agent in animal models of carcinogenesis and in patients with familial adenomatous polyposis. Because tumor promotion is generally associated with exposure to pro-inflammatory stimuli, it is likely that anti-inflammatory agents may have potent antitumor effects. In human skin, sulindac reduces bradykinin-induced edema. In this study, we tested the hypothesis that the cyclooxygenase inhibitor sulindac can protect against ultraviolet (UVB)-induced injury that is crucial for the induction of cancer. Exposure of SKH-1 hairless mice to two consecutive doses of UVB (230 mJ/cm2) induces various inflammatory responses including erythema, edema, epidermal hyperplasia, infiltration of polymorphonuclear leukocytes, etc. Topical application of sulindac (1.25-5.0 mg/0.2 ml acetone) to the dorsal skin of SKH-1 hairless mice either 1 h before or immediately after UVB exposure substantially inhibited these inflammatory responses in a dose-dependent manner. Oral administration of sulindac in drinking water (160 ppm) for 15 days before and during UVB irradiation similarly reduced these inflammatory responses. These potent anti-inflammatory effects of sulindac suggested the possibility that the drug could inhibit signaling processes that relate to carcinogenic insult by UVB. Accordingly, studies were conducted to assess the efficacy of sulindac in attenuating the expression of UVB-induced early surrogate molecular markers of photodamage and carcinogenesis. UVB exposure enhanced the expression of p53, c-fos, cyclins D1 and A, and PCNA 24 h after irradiation. Treatment of animals with either topical or oral administration of sulindac largely abrogated the expression of these UVB-induced surrogate markers. These results indicate that the cyclooxygenase inhibitor sulindac is effective in reducing UVB-induced events relevant to carcinogenesis and that this category of topically applied or

  14. Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population

    Sameer A

    2011-07-01

    Full Text Available Abstract The development and progression of colorectal cancer (CRC is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR. The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86. Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86 of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05. Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

  15. Classical presentation of Gardner's syndrome in an Indian patient: A case report

    Priyanka Verma; Varun Surya; Sonali Kadam; Umarji, Hemant R.

    2016-01-01

    Gardner's syndrome is an autosomal dominant disease characterized by the presence of colonic polyposis, osteomas, and a multitude of soft-tissue tumors. Dental anomalies are present in estimated 30% of all affected individuals of Gardner's syndrome, so dental professionals play an important role in determining the early signs of the syndrome. The intestinal polyps have a 100% risk of undergoing malignant transformation if not treated thus, early diagnosis and regular surveillance are importan...

  16. Patients' preferences for patient-centered communication

    Lau, Sofie Rosenlund; Christensen, Søren Troels; Andreasen T., Jesper

    2013-01-01

    To investigate patients' preferences for patient-centered communication (PCC) in the encounter with healthcare professionals in an outpatient department in rural Sierra Leone.......To investigate patients' preferences for patient-centered communication (PCC) in the encounter with healthcare professionals in an outpatient department in rural Sierra Leone....

  17. [Patient advice].

    Lucio-Villegas Menéndez, M Eulalia; González, Laura López; Gutiérrez Pérez, M Isabel; Lluch, Natalia Aresté; Morató Agustí, M Luisa; Cachafeiro, Santiago Pérez

    2014-05-01

    In wound care, knowing what to do is as important as knowing what not to do. The first step is to evaluate the severity of the lesion and to know whether it is necessary to attend a health center or not. If the wound is simple, the recommended course of action is cleansing with serum or water after washing one's hands, followed by wound disinfection with the most appropriate antiseptic. Antiseptics not should be used for wound cleansing (physiological serum or tap water should be used) or for wound healing with granulation tissue. Equally, antiseptics should not be used in the ear or near the eyes; if there is accidental application, the eye should be washed in abundant water. Povidone iodine should not be used in pregnant women, nor should iodine preparations be used in neonates, in patients with thyroid alterations or in those allergic to iodine. Currently, merbromine/mercurochrome is not used because of its mercury content. Before an antiseptic is applied, all inorganic residues (foreign bodies) and dead tissue should be removed; detritus, slough, purulent exudate, scabs… This will aid healing and the action of antiseptics, since they become inactive in the presence of organic material. PMID:24998084

  18. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

    Victoria Gonzalo; Juan José Lozano; Jenifer Muñoz; Francesc Balaguer; Maria Pellisé; Cristina Rodríguez de Miguel; Montserrat Andreu; Rodrigo Jover; Xavier Llor; M Dolores Giráldez; Teresa Ocaña; Anna Serradesanferm; Virginia Alonso-Espinaco; Mireya Jimeno; Miriam Cuatrecasas

    2010-01-01

    BACKGROUND: Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-...

  19. Periodontitis in HIV patients

    Oseeva А.О.; Soboleva L.A.; Bulkina N.V.; Shuldyakov A.A.

    2011-01-01

    The article presents the study of formation mechanisms and periodontitis course in patients with subclinical stage of HIV-infection. The examination of 45 patients has enabled the division of patients into three basic groups: patients with periodontitis and HIV-infection; patients with periodontitis; and HIV patients without periodontitis. It has been determined that the patients with periodontitis and subclinical HIV-infection have developed local inflammatory reaction with infection, activa...

  20. Patient-centered Radiology.

    Itri, Jason N

    2015-10-01

    Patient-centered care (ie, care organized around the patient) is a model in which health care providers partner with patients and families to identify and satisfy patients' needs and preferences. In this model, providers respect patients' values and preferences, address their emotional and social needs, and involve them and their families in decision making. Radiologists have traditionally been characterized as "doctor-to-doctor" consultants who are distanced from patients and work within a culture that does not value patient centeredness. As medicine becomes more patient driven and the trajectory of health care is toward increasing patient self-reliance, radiologists must change the perception that they are merely consultants and become more active participants in patient care by embracing greater patient interaction. The traditional business model for radiology practices, which devalues interaction between patients and radiologists, must be transformed into a patient-centered model in which radiologists are reintegrated into direct patient care and imaging processes are reorganized around patients' needs and preferences. Expanding radiology's core assets to include direct patient care may be the most effective deterrent to the threat of commoditization. As the assault on the growth of Medicare spending continues, with medical imaging as a highly visible target, radiologists must adapt to the changing landscape by focusing on their most important consumer: the patient. This may yield substantial benefits in the form of improved quality and patient safety, reduced costs, higher-value care, improved patient outcomes, and greater patient and provider satisfaction. PMID:26466190

  1. Burns in diabetic patients

    Maghsoudi, Hemmat; Aghamohammadzadeh, Naser; Khalili, Nasim

    2008-01-01

    CONTEXT AND AIMS: Diabetic burn patients comprise a significant population in burn centers. The purpose of this study was to determine the demographic characteristics of diabetic burn patients. MATERIALS AND METHODS: Prospective data were collected on 94 diabetic burn patients between March 20, 2000 and March 20, 2006. Of 3062 burns patients, 94 (3.1%) had diabetes; these patients were compared with 2968 nondiabetic patients with burns. Statistical analysis was performed using the statistical...

  2. The Angry Dying Patient

    Houston, Robert E.

    1999-01-01

    Over 25 years ago, Kubler-Ross identified anger as a predictable part of the dying process. When the dying patient becomes angry in the clinical setting, all types of communication become strained. Physicians can help the angry dying patient through this difficult time by using 10 rules of engagement. When physicians engage and empathize with these patients, they improve the patient's response to pain and they reduce patient suffering. When physicians educate patients on their normal response...

  3. Patient-centred Prevention among PAD Patients

    Pii, Kathrine Hoffmann

    2014-01-01

    Intro: This paper discusses a central professional dilemma in patient-centred education: on one hand the concern for ensuring patients autonomy and right to make their own decisions regarding their treatment and, on the other hand, a concern for getting patients to make the “right” decisions that...... will improve their health condition. The patient-centred approach (and related concepts: patient participation, involvement, and empowerment) is being promoted both in healthcare politics and by healthcare professionals as a way to achieve more active self-managing and self-caring patients. Patient......-centredness is thus promoted as a way to organize health more effectively (in terms of cost and treatment outcomes) and as a way to ensure patients’ autonomy and fundamental right to make their own decisions regarding their treatment. Critical voices within social and nursing theory have however argued that the...

  4. Patient Assessment File (PAF)

    Department of Veterans Affairs — The Patient Assessment File (PAF) database compiles the results of the Patient Assessment Instrument (PAI) questionnaire filled out for intermediate care Veterans...

  5. Transfer Out Patient Not Abandon The Patient

    Deepak Gupta

    2015-12-01

    Full Text Available Physician-patient relationship is unique in some aspects and not-so-unique in other aspects when compared to other human interactions. Until-unless for the sake of health promotional activities, this relationship is almost always conceived in the times of human sufferings and consequently culminated when those sufferings have subsided as well as sought out happiness has ensued/been achieved. However, not all physician-patient relationships follow the normal course and/or meet the natural ends. These abnormal relationships are not inconsequential in terms of numbers and/or their effects (short-term and long term on both patients and physicians. Every country has its own baggage in the wake of why, how and what about these abnormal ends to physician-patient relationships; however, the most common causes are the patients’ inability to pay their medical bills, the conflicting goals of physicians and their patients in regards to patients’ sufferings’ management and finally the behavioral issues (patients’ and/or physicians’ interfering these relationships. Irrespective of any cause, the physicians should never forget that the patient can always discharge their physicians and discontinue their relationship with their physicians without any reason (until unless the physicians deem those patients either incapable/non-consentable to do so and/or potential threat to their own personal safety or other people’s safety. Contrarily, physicians can also discharge patients from their care but cannot abandon these patients (1-3 which mean that physicians have to ensure their discharged patients either are referred to or have sought another physician within appropriate time frame post-relationship-discontinuation. Each country has their own medico-legal liabilities that vary in terms of penalties imposed; however, irrespective of the feared legal concerns, the physicians should not forget that ethical essence of medicine is the art of healing that

  6. Surgical considerations in FAP-related pouch surgery: Could we do better?

    Möslein, Gabriela

    2016-07-01

    The ileoanal pouch has become the standard restorative procedure of choice for patients with the classical phenotype in FAP (familial adenomatous polyposis) and also for ulcerative colitis (UC). Whilst we tend to encounter descriptive analyses comparing functional outcome, fertility and quality of life (QOL) between series in literature, there may be an urgent need to discuss the subtle technical modifications that may be pivotal for improving long-term QOL in FAP patients. Our aim is to review the current literature and discuss the aspects of ileal pouch-anal anastomosis that may require specific reevaluation for FAP. Surgical strategies aimed at minimizing post-interventional desmoid growth is one of the most important aspects. For this study, the following topics of interest were selected: Timing of surgery, IRA or ileoanal pouch for classical FAP, laparoscopic or conventional surgery, TME or mesenteric dissection, preservation of the ileocolic vessels, handsewn or double-staple anastomosis, shape and size of pouch, protective ileostomy, Last and definitely not least: how to manage desmoid plaques or desmoids at the time of prophylactic surgery. For the depicted technicalities of the procedure, a review of recent literature was performed and evaluated. For the topics selected, only sparse reference in literature was identified that was focused on the specific condition situation of FAP. Almost all pouch literature focusses on the procedural aspects, and FAP patients are always a very minor number. Therefore it becomes obvious that the specific entity is not adequately taken into account. This is a serious bias for identification of important steps in the procedure that may be beneficial for patients with either of the diseases. The results of this study demonstrate that several technical differences for construction of ileoanal pouches in FAP patients deserve more attention and prospective evaluation-perhaps even randomized trials. The role, importance and

  7. [Ambulatory surgery. Patients and patient education].

    Bredland, T; Duesund, R

    1996-02-20

    This article reviews the concept of day surgery and shows how the treatment can be organized pre-, per- and post-operatively. It can be established in a hospital-integrated unit, a unit separate from the hospital, but connected with it, or a satellite ambulatory facility. Because the patient spends only a short time in hospital it is necessary to have structured preparations before admission, for the benefit of both patient and staff. It should be easy to identify patients suitable for day surgery from the waiting lists, and preparations should be directed at treatment by day surgery right from the start. Rules must be worked out for selecting patients, as well as guidelines for information to patients. It is also necessary to plan the operation programme, and to agree how nurses and doctors should take care of the patient during the different steps of treatment. PMID:8658453

  8. A good patient?

    Campbell, Catherine; Scott, Kerry; Skovdal, Morten;

    2015-01-01

    , physical cleanliness, honesty, gratitude and lifestyle adaptations (taking pills correctly andcoming to the clinic when told). As healthcare workers may decide to punish patients who do not live up the‘good patient persona’, many patients seek to perform within the confines of the ‘good patient persona’ to...

  9. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  10. Displacing the patient

    Pors, Anja Svejgaard

    2014-01-01

    target groups for which information can be standardized. In the latter approach (market orientation), the patient is also a resource for organizational development. Overall, the strategy presents an information-pursuing patient figure that makes it possible to streamline the organization's care...... in Copenhagen, Denmark. Based on situational analysis of internal documents, the paper gives an empirical account of the work of strategic documents and explores how the documents organize patient communication through displacements of the patient. This paper shows that the hospital’s patient...... communication is not only about disease treatment, but also about ‘information treatment’ for the purpose of increasing patient satisfaction at the hospital. The goal of patient satisfaction addresses both a care-oriented approach to the patient and also deploys market perceptions of patients as homogeneous...

  11. Displacing the Patient

    Pors, Anja Svejgaard

    as an affective care recipient, as a citizen with rights and as an individual need-oriented user on the one hand. On the other hand, the goal of patient satisfaction also deploys market perceptions of patients as homogeneous target groups to which information can be standardised. In the latter......The analysis is based on an empirical study of a hospital’s communication strategy entitled: 'The Perspective of the Patient'. The paper asks how the strategy organizes communication work as situated displacements of the patient. Based on methodological elements from situational analysis (Clarke...... 2005) the analysis examines how the hospital’s patient communication is not just about disease treatment, but rather about information treatment of the patient in order to attain a high level of patient satisfaction. The goal of patient satisfaction addresses care-oriented understandings of the patient...

  12. Displacing the patient

    Pors, Anja Svejgaard

    2012-01-01

    a care-oriented approach to the patient and also deploys market perceptions of patients as homogeneous target groups to which information can be standardized. In the latter approach (market orientation), the patient is also a resource for organizational development. Overall, the strategy presents an......This analysis is based on an empirical study of a Danish hospital‟s communication programme entitled: 'The Perspective of the Patient'. The paper explores how strategic documents of the programme organize the communication work through situated displacements of the patient. Based on methodological...... elements from situational analysis (Clarke 2005) the analysis examines how the hospital‟s patient communication is not only about disease treatment, but rather about information treatment of the patient in order to attain a high level of patient satisfaction. The goal of patient satisfaction addresses both...

  13. A Clinical Study on 125IT3 Resin Uptake Rate and Serum Thyroxin(T4) in Hyperthyroidism

    Hyperthyroidism may be defined as those clinical conditions which result from an increase in the circulating levels of one or both thyroid hormones. Hyperthyroidism in broad sense could be classified with toxic diffuse goiter, toxic adenomatous goiter, and toxic multinodular goiter on the basis of the circulating thyroid hormone levels. For this study, the subject included 94 cases with hyperthyroidism were presented in 77 with toxic diffuse goiter, 8 with toxic adenomatous goiter, and 9 with toxic multinodular goiter on the levels of 125IT3 resin uptake rate and serum thyroxine (T4). The observed results were as follows: 1) In the cases of hyperthyroidism including toxic diffuse goiter, toxic adenomatous goiter, and toxic multinodular goiter, 20.21% of the patients were male and 79.79% female. The majority of the patients were in 2nd to 4th decades of their lives. 2) There were objective signs clearly manifested in hyperthyroidism including toxic diffuse goiter and toxic adenomatous goiter which were rare in the multinodular goiter. The clinical signs in toxic diffuse and toxic adenomatous goiter included wide pulse pressure, tachycardia, systolic murmur, exophthalmos, tremor and warm skin etc. 3) The most frequent complaints of the patients with hyperthyroidism were palpitation, weight loss, increased appetite, perspiration, heat intolerance, nervousness, exertional dyspnea, and menstrual disturbance etc. There was no clear difference in the incidence of symptoms between toxic diffuse goiter and toxic adenomatous goiter, but there was clear difference between toxic multinodular goiter. 4) Considering of results of 125IT3 resin uptake rate and serum T4 level in toxic diffuse goiter, toxic adenomatous goiter and toxic multinodular goiter, 125IT3 resin uptake rate was 49.15±9.94% (mean) and serum T4 21.29±7.04 ug/dl (mean) in toxic diffuse goiter. In toxic multinodular goiter, 125I T3 resin uptake rate was 32.47±6.74% (mean) and serum T4 level 11.03±5.0 ug

  14. Multiple Myeloma: Patient Handbook

    ... contact us TEXT SIZE IMF Multiple Myeloma Patient Handbook 2016 One of the most daunting aspects of ... with each of these steps. The IMF’s Patient Handbook is meant to furnish you with the tools ...

  15. National Patient Safety Foundation

    ... Professional Learning Series Webcasts CPPS Review Course E-Learning Patient Safety Curriculum CPPS Review Course Patient Blood Management Reducing Diagnostic Error Health Info Technology Publications Ask Me 3 For ...

  16. Patient life in hospital

    Ludvigsen, Mette Spliid

    Patient life in hospital.A qualitative study of informal relationships between hospitalised patients Introduction Within a patientology framework, this PhD dissertation is about an empirical study on patient life that provides insight into the nature of informal relationships between patients in...... hospitals today. Purpose The purpose was to explore how informal relationships between patients affect their hospital experiences in the hospital. The assumption is that, on the one hand, the impacts on patients' suffering affect the way they act and experience encounters with fellow patients for good or....... Methods The study is designed within a phenomenological-hermeneutical philosophic frame of reference and is based on ethnographic fieldwork among hospitalised patients in a Danish university hospital. Data for the study were collected through participant observations over a period of 18 months. Nine males...

  17. Lejringsskader hos rygopererede patienter

    Sestoft, Bodil; Larsen, Birgit; Erlandsen, Mogens;

    2009-01-01

    INTRODUCTION: The aim of this study was to answer the questions: Which kind of positioning injuries occurred in anaesthetized orthopaedic patients undergoing spine surgery who were prone-positioned for more than two hours? What was the incidence of positioning injuries? Which patients were at...... particular risk of developing positioning-related injuries? MATERIAL AND METHODS: Follow-up study comprising 299 patients. A patient record followed the patient from the day of surgery until discharge. Selected pre-disposing factors related to positioning injuries as well as positioning-related injuries were...... registered. One year after surgery, localisation, duration and treatment of positioning-related injuries were registered. A total of 299 patients were included. Among these, 60 patients died within the first year, and 52 could not be reached. The remaining 187 patients were interviewed by telephone one year...

  18. Multiple Myeloma: Patient Handbook

    ... of these new biomarkers can indepen- dently pred ict that a patient with SMM has an 80% ... stop or adjust doses on your own. Patient education sheets on preventing blood clots and thromboembolic events, ...

  19. Learning from patients

    Henriksen, Ann-Helen; Ringsted, Charlotte

    2011-01-01

    Prior research on the use of patients as teachers has focused on testing the effectiveness of this practice and exploring its benefits for students. However, very little is known about the added value of patient teaching and how it relates to patient-centred learning. The aim of this study was to...

  20. Patients Provide Recommendations for Improving Patient Satisfaction.

    Moore, Angelo D; Hamilton, Jill B; Krusel, Jessica L; Moore, LeeAntoinette G; Pierre-Louis, Bosny J

    2016-04-01

    National Committee for Quality Assurance recommends patient-centered medical homes incorporate input from patient populations; however, many health care organizations do not. This qualitative study used two open-ended questions from 148 active duty Army Soldiers and their family members to illicit recommendations for primary care providers and clinic leadership that would improve their health care experiences. Content analysis and descriptive statistics were used to analyze responses. Participant responses were related to four major themes: Access to Care, Interpersonal Interaction, Satisfaction of Care, and Quality of Care. Participants were overall satisfied with their care; however, spending less time waiting for appointments and to see the provider or specialist were the most frequently requested improvements related to Access to Care. For Interpersonal Interaction, 82% of the responses recommended that providers be more attentive listeners, courteous, patient, caring, and respectful. Decreasing wait times and improving interpersonal skills would improve health care experiences and patient satisfaction. PMID:27046182

  1. Unilateral chest wall anomaly in a patient with Gardner' s syndrome: A case report

    Song, Eun Hee; Lee, So Yeon; Park, Hee Jin; Kwon, Heon Ju; Kim, Mi Sung; Park, Hae Won; Kwang, Hyon Joo [Dept. of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Hye Jin [Dept. of Radiology, Eulji General Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of)

    2014-05-15

    Gardner syndrome is a familial disease consisting of colonic polyposis, osteomas, and soft tissue tumors. We describe unilateral chest wall anomaly in a 32-year-old man with Gardner syndrome. A chest radiograph showed asymmetric hypertrophy of the right seventh to tenth ribs. CT images showed increased size of the medullary portions of these lesions, but relatively normal thickness of the cortex. Intercostal muscles along the right seventh to tenth ribs were hypertrophied as compared with the contralateral ribs. Both lungs were clear but the volume of right lung showed slightly smaller than left one.

  2. Tumores colorretais hereditários Hereditary colorectal tumors

    Benedito Mauro Rossi

    1998-08-01

    áveis pela respectiva doença ou pela proteína produto dos mesmos. É de suma importância uma abordagem multidisciplinar de pacientes portadores de FAP ou HNPCC, pois existe uma preocupação ética muito grande na realização dos testes genéticos de predisposição, considerando suas conseqüências psicológicas e sociais.About 15% of the colorectal tumors are hereditary. There are two main groups: the familiar adenomatous polyposis (FAP and the non-polyposis colorectal cancer (HNPCC, both autosomal dominant diseases. Patients with FAP present hundreds to thousands of adenomas in colorectum. usually after puberty. The cause of FAP is mutation of the adenomatous polyposis coli (APC gene, located on long arm of chromosome 5 (5q. Patients who have not undergone to colectomy, the only treatment avaiable, will develop colorectal cancer and die at the age of 45 years. Extracolonic manifestations can occur: gastric and small bowel adenomas, soft tissue tumors, retinal pigmentation. osteomas. Patients with HNPCC do not present hundreds of benign polyps, but already a solitary colorectal cancer: This disease is caused by mutations in one of the several mismatch repair genes (hMSH2, hMLHI, hPMSI, hPMS2, hPMS6/GTBP. The average age of the diagnosis is 45 years and usually the disease produces cancer in the right colon. Other carcinomas can occur: endometrial, stomach, pancreas and others. Prophylactic surgery in asymptomatic gene carriers are controversial. Nowadays it is possible to identify asymptomatic genes carriers of FAP and HNPCC by genetic testing. The analysis can be done by direct gene sequencing or by in vitro synthesized protein assay (IVSP, which finds defective truncate proteins. Genetic testing for hereditary forms of colorectal cancer requires not only an appropriate laboratory, but genetic counseling with an ethical multidisciplinary approach considering the psychological and social consequences.

  3. Can patients educate patients? A feasibility study

    Curtis, Ffion; Hurlin, Claire; Tomlinson, Sarah; Thatcher, Rhys; Rice, Sam

    2016-01-01

    Aims and Objectives: To assess the feasibility of conducting a randomised control trial to evaluate the effectiveness of a patient delivered education programme for Type 2 diabetes in a Welsh population and to explore a range of factors that could inform future delivery of such a programme. Design: A randomised case control study was deployed. 60 newly diagnosed Type 2 diabetes patients were recruited (40 into a treatment arm and 20 into a control arm). Participants were randomly allocated...

  4. The Epidemiological and Clinical Aspects of Nasal Polyps that Require Surgery

    Ahmad Meymane Jahromi

    2011-01-01

    Full Text Available Introduction: The objective of this retrospective cross-sectional study was to obtain epidemiological data from the charts of 297 patients with nasal polyposis who were operated on in a referral hospital in Mashhad and to determine the frequency of the presenting symptoms of nasal polyps.  Materials and Methods: The variables recorded included age, gender, the presence of asthma or allergic rhinitis, family history, and previous treatments. We studied the main symptoms of nasal polyposis (nasal obstruction, rhinorrhea, anosmia, headache, epistaxis, snoring, and so on, as well as ear problems and facial deformity.  Results: Nasal polyposis affects men (60.3% more frequently, at a mean age of 39.5 years. The most frequent symptom was nasal blockage (81.1 % followed by rhinorrhea (37.7%. A total of 11.1% of the patients had a history of epistaxis. Asthma was found in 10.4% of patients with nasal polyposis and the ears were affected in 5.1% of patients. In all, 7.4% of patients had first-degree relatives who suffered from asthma or allergic rhinitis.  Conclusion: This study highlights the need for large-scale epidemiologic research exploring the prevalence and incidence of nasal polyposis in Iran.

  5. 288 IL1B but not IL8 Polymorphisms Are Increased in Aspirin Exacerbated Respiratory Disease Patients Versus Aspirin Tolerant Asthmatics

    Pavon Romero, Fernando Gandhi; Falfán-Valencia, Ramcés; Camarena, Angel; Garcia Cruz, Ma de la Luz; Terán-Juarez, Luis Manuel

    2012-01-01

    Background Aspirin exacerbated respiratory disease (AERD) is a syndrome characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma and aspirin sensitivity. The mechanisms by which produce these manifestations of intolerance are not fully defined, the current research involve alterations in the metabolism of arachidonic acid, cyclooxygenase 1 (COX-1) inhibition and its deviation from substrate to the lipoxygenase (LO) pathway, inducing increased synthesis of leukotrienes (LT...

  6. Periodontitis in HIV patients

    Oseeva А.О.

    2011-09-01

    Full Text Available The article presents the study of formation mechanisms and periodontitis course in patients with subclinical stage of HIV-infection. The examination of 45 patients has enabled the division of patients into three basic groups: patients with periodontitis and HIV-infection; patients with periodontitis; and HIV patients without periodontitis. It has been determined that the patients with periodontitis and subclinical HIV-infection have developed local inflammatory reaction with infection, activation of anti-inflammatory cytokines in parodontal recess fluid. It has been proved that the causative factor of frequent and durable relapses in parodontal pathology with clinical HIV-infection was the development of pathologic process with endotoxicosis syndrome and imbalance of lipid peroxidation and antioxidant system

  7. Patient-centered Care.

    Reynolds, April

    2009-01-01

    Patient-centered care focuses on the patient and the individual's particular health care needs. The goal of patient-centered health care is to empower patients to become active participants in their care. This requires that physicians, radiologic technologists and other health care providers develop good communication skills and address patient needs effectively. Patient-centered care also requires that the health care provider become a patient advocate and strive to provide care that not only is effective but also safe. For radiologic technologists, patient-centered care encompasses principles such as the as low as reasonably achievable (ALARA) concept and contrast media safety. Patient-centered care is associated with a higher rate of patient satisfaction, adherence to suggested lifestyle changes and prescribed treatment, better outcomes and more cost-effective care. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your area of interest. For access to other quizzes, go to www.asrt.org/store. According to one theory, most patients judge the quality of their healthcare much like they rate an airplane flight. They assume that the airplane is technically viable and is being piloted by competent people. Criteria for judging a particular airline are personal and include aspects like comfort, friendly service and on-time schedules. Similarly, patients judge the standard of their healthcare on nontechnical aspects, such as a healthcare practitioner's communication and "soft skills." Most are unable to evaluate a practitioner's level of technical skill or training, so the qualities they can assess become of the utmost importance in satisfying patients and providing patient-centered care.(1). PMID:19901351

  8. GASTROINTESTINAL MALIGNANCIES: GETTING A DECADE YOUNGER?

    Sushmitha

    2014-06-01

    were studied with 98 cases in upper GI and 30 cases in lower GI. Out of the 98 upper GI malignancies, 36 were from oesophagus, 57 were from stomach and 5 were from the duodenum. Out of the 36 oesophageal malignancies, 13(36% were in patients less than fifty years of age. However the gastric carcinomas were more in patients over fifty years. Colorectal malignancies were higher in <50 years age group i.e. 15 out of 30 cases (50%. CRC in the present study has male: female ratio of 1: 1.5.26% of carcinoma in young shows positive family history. 3 out of 15 (20% carcinoma in young show polyps. Incidence of familial carcinoma is higher between 20- 40 years of age. Out of 4 cases with positive family history, one is FAP (familial adenomatous polyposis and 2 are Lynch syndrome with second malignancies in ovaries

  9. The ins and outs of APC and β-catenin nuclear transport

    Henderson, Beric R.; Fagotto, Francois

    2002-01-01

    Adenomatous polyposis coli (APC) and β-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a β-catenin chaperone. Here, we review the regulation of APC and β-catenin subcellular localization, in particular in cancer cells. We speculate that, in non-stimulated cells, APC actively exports β-catenin from the nucleus to the cytoplasm where its levels are regulated by degradation; and, conversely, that, in cancer cells or those stimulated by Wnt signaling, β-catenin degradation is inhibited and the accruing protein is capable of moving between the nucleus and cytoplasm independently of APC. Models that link APC and β-catenin transport to function are discussed. PMID:12223464

  10. The ins and outs of APC and beta-catenin nuclear transport.

    Henderson, Beric R; Fagotto, Francois

    2002-09-01

    Adenomatous polyposis coli (APC) and beta-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a beta-catenin chaperone. Here, we review the regulation of APC and beta-catenin subcellular localization, in particular in cancer cells. We speculate that, in non-stimulated cells, APC actively exports beta-catenin from the nucleus to the cytoplasm where its levels are regulated by degradation; and, conversely, that, in cancer cells or those stimulated by Wnt signaling, beta-catenin degradation is inhibited and the accruing protein is capable of moving between the nucleus and cytoplasm independently of APC. Models that link APC and beta-catenin transport to function are discussed. PMID:12223464

  11. Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors

    Huiling Xu

    2014-12-01

    Full Text Available Loss of heterozygosity (LOH of the adenomatous polyposis coli (APC gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC. We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1 retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.

  12. Prophylaxis against colorectal cancer

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a...... well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials for...... colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  13. Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer.

    Fancy, Stephen P J; Harrington, Emily P; Baranzini, Sergio E; Silbereis, John C; Shiow, Lawrence R; Yuen, Tracy J; Huang, Eric J; Lomvardas, Stavros; Rowitch, David H

    2014-04-01

    In colon cancer, mutation of the Wnt repressor APC (encoding adenomatous polyposis coli) leads to a state of aberrant and unrestricted high-activity signaling. However, the relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct functional states of Wnt activity determine oligodendrocyte precursor cell (OPC) differentiation and myelination. Mouse OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer, including Lef1, Sp5, Ets2, Rnf43 and Dusp4. Surprisingly, we found that OPCs in lesions of hypoxic human neonatal white matter injury upregulated markers of high Wnt activity and lacked expression of APC. We also found that lack of Wnt repressor tone promoted permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack predisposing genetic mutation. PMID:24609463

  14. Prophylaxis against colorectal cancer

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  15. Involvement of CDX2 in the cross talk between TNF-α and Wnt signaling pathway in the colon cancer cell line Caco-2

    Coskun, Mehmet; Olsen, Anders Krüger; Bzorek, Michael;

    2014-01-01

    Tumor necrosis factor-α (TNF-α) is highly upregulated in inflammation and reduces the expression of the intestinal transcription factor, Caudal-related homeobox transcription factor 2 (CDX2). Wnt/β-catenin signaling is critical for intestinal cell proliferation, but a decreased CDX2 expression has...... the signaling pathways involved in the TNF-α-mediated downregulation of CDX2, and its influence on Wnt/β-catenin signaling components in colon cancer cells. The expression of TNF-α and CDX2 at the invasive front were evaluated by immunohistochemical staining and showed reduced CDX2-positive cells in...... are involved in the TNF-α-dependent downregulation of CDX2. Furthermore, TNF-α-mediated downregulation of CDX2 was found to significantly decrease the mRNA levels of adenomatous polyposis coli (APC), axis inhibition protein 2 (AXIN2) and glycogen synthase kinase-3 beta (GSK3β), whereas the mRNA levels...

  16. Depression in Cancer Patients

    Beyhan Bag

    2014-06-01

    Full Text Available It is not enough to consider treatment and care depression in the oncology that is the most common psychiatric illness in cancer patient affects of cancer treatment and the patient`s quality of life negatively, which is determined through researches in the field. With development of psycho-oncology it has been demonstrated to establish an important link between the cancer patient`s treatment as well as psycho-social support for the patient and psychiatric treatment and care for the if it is needed. With this connection between them it has been proposed to use of bio-psycho-social-model in cancer patient to improve their care. To achieve this goal, it is expected from medical personnel to realize patients psychosocial need und if he/she has a psychiatric disorders or syndromes. For the medical personnel that work in oncology services, it is inevitable to organize in order to raise the awareness of depression in the cancer patients. In the present study, it is focused on raising the awareness of depression in cancer patient for the medical personnel. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 186-198

  17. Patient Education Among Stroke Survivor Patients

    Martin, Ruth

    2014-01-01

    Stroke is one of the most serious health problems in the world, cited as being the second leading cause of death. After stroke, there is a greater risk of suffering second and further subsequent stroke-events. Given the heavy burden of disease present by stroke, there is a great need to improve patient education for stroke survivors, who are at an increased risk of another cerebrovascular accident. The purpose of this thesis is to develop the quality of patient education in nursing care o...

  18. Music for Hemodialysis patients

    Gross, B; Ketema Wassie, F; Agnholt, Hanne;

    Music for hemodialysis patients Background Patients starting a new regimen of dialysis often experience anxiety and other psychological disturbances. They struggle with the unknown situation, feelings of uncertainty and on top of that, a high level of sophisticated technological equipment. Music...... is known from literature to influence and dampen anxiety and tension and has been used for millennia in the treatment of illness. Here we report a study on the influence of music on patients undergoing dialysis and whether music has a potential for lowering discomfort in patients during first-time dialysis.......   Purpose To investigate whether music can reduce feelings of anxiety, tension and restlessness in patients new to dialysis treatment and make them more relaxed during the treatment.   Method Twenty patients aged 42-84 were selected for participation in the study, which took place over two separate dialysis...

  19. [Two patients with mumps].

    van Brummelen, S E; de Vries, E; Schneeberger, P M; van Binnendijk, R S; Lestrade, P; Wever, P C

    2006-08-01

    Two patients, men aged 17 and 19 years respectively, were admitted with parotitis epidemica and orchitis caused by mumps. The second patient also had meningitis. PCR analysis revealed that, in both cases, the causative agentwas a mumps virus that was genetically related to a wild-type virus responsible for an outbreak in Singapore. This viral strain was also responsible for a mumps outbreak at Hotel School The Hague in September 2004. Both patients were not fully vaccinated. Both patients were from regions in which clustering of patients with clinical signs of mumps has been seen. Interestingly, a number of patients with confirmed mumps had been fully vaccinated. Possible explanations for the increase in mumps cases include low vaccination and immunity levels, primary and secondary vaccine failure and the emergence of genetically disparate mumps viruses. PMID:16924947

  20. Patient Safety Executive Walkarounds

    Feitelberg, Steven P

    2006-01-01

    The KP Patient Safety Executive Walkarounds Program in the KP San Diego Service Area was developed to provide routine opportunities for senior KP leaders, staff, and clinicians to discuss patient safety concerns proactively, working closely with our labor partners to foster a culture of safety that supports our staff and physicians. Throughout the KP San Diego Service Area, the Walkarounds program plays a major part in promoting responsible identification and reporting of patient safety issue...

  1. Dental Patient Robot

    Takanobu, Hideaki

    2008-01-01

    A patient robot with an oral cavity mimicking unexpected movement due to vomiting and pain and functions to induce bleeding and saliva flow was developed and used for clinical training. Trainee students and clinical residents were asked to complete a questionnaire about the patient robot. The results showed the patient robot to be effective as a means of training students to respond to unexpected movements during surgical procedures. In the future, the author intend to incorporate additional ...

  2. Sygepleje til trakeostomerede patienter

    Christensen, Dorthe Wiinholdt; Andersen, Rene Richard; Rydahl-Hansen, Susan

    2016-01-01

    Between 50 and 83 per cent of patients with a tracheostomy have difficulty swallowing. A study comprising 553 patients found aspiration and silent aspiration in respectively 48.8 per cent and 36.8 per cent of patients. As aspiration into the lungs is the commonest cause of hospital-acquired infec......Between 50 and 83 per cent of patients with a tracheostomy have difficulty swallowing. A study comprising 553 patients found aspiration and silent aspiration in respectively 48.8 per cent and 36.8 per cent of patients. As aspiration into the lungs is the commonest cause of hospital...... fluid/food when the tracheostomy is cuffed; whether nurses should ideally test patients for mis-swallowing and the extent to which nurses can prevent mis-swallowing. A systematic review showed that it makes a difference whether the patient is cuffed or uncuffed when fluid/food is administered. We also...... found a number of tools suitable for use in testing for dysphagia. We still do not know whether dysphagia can be prevented in tracheostomy patients, as we did not find answers to this question in the scientific literature.....

  3. Acknowledging the back patient

    Damsgaard, Janne Brammer; Bastrup, Lene; Norlyk, Annelise; Birkelund, Regner

    back patient and what back patients consider important when dealing with the healthcare system. Methods: The method draws on James Thomas' and Angela Hardens approach in "Methods for the thematic synthesis of qualitative research in systematic reviews" (2008). The thematic synthesis aims to systematise...... and integrate findings of qualitative studies. Results: The analysis reveals that many back patients feel that their experiences and perceptions are ignored by the health professionals, who are often concerned about identifying the cause. This can result in patients feeling mistrusted, marginalised...

  4. Excluding the typical patient

    Odlaug, Brian Lawrence; Weinhandl, Eric; Mancebo, Maria C;

    2014-01-01

    Over the past 30 years, clinical trials have resulted in several successful pharmacotherapies for obsessive-compulsive disorder (OCD), yet patients in clinical settings often report inadequate response. This study compares clinical characteristics of treatment-seeking OCD patients to the inclusion...

  5. Caring for transgender patients.

    Abebe, Alyssa

    2016-06-01

    Clinicians need a better understanding of transgender populations and a systematic approach to treating transgender patients medically and psychologically while managing any potential judgment or bias. This article explains key concepts, describes transgender patient health concerns, and discusses how to perform a comprehensive history. PMID:27228044

  6. Withholding truth from patients.

    O'Sullivan, Elizabeth

    2012-01-31

    The issue of whether patients should always be told the truth regarding their diagnosis and prognosis has afforded much debate in healthcare literature. This article examines telling the truth from an ethical perspective. It puts forward arguments for and against being honest with patients, using a clinical example to illustrate each point.

  7. Dyspnea in dying patients.

    Hsu, D H

    1993-01-01

    Dyspnea is common in terminally ill patients and is often fairly difficult to control. If specific causes cannot be identified or treated, general measures to relieve symptoms should be used. Nondrug measures (eg, discussion and explanation with the patient) and drug measures (eg, morphine) can be used to control the dyspnea, although side effects, such as sedation, can be problematic.

  8. Approach to bleeding patient

    Ramachandran Gopinath

    2014-01-01

    Full Text Available Managing a bleeding patient is very challenging for the perioperative physician. Bleeding in a patient would be due to inherited or acquired disorders of haemostasis. Identifying the patients at risk of bleeding and utilising prophylactic treatment protocols has good outcomes. Along with clinical signs, trends in monitoring coagulation parameters and analysing blood picture are necessary. Management of patients in the postoperative period and in intensive care unit should be focused on normalization of coagulation profile as early as possible with available blood and its products. Available recombinant factors should be given priority as per the approved indications. Exploring the surgical site should be considered for persistent bleeding because haemodynamic compromise, excessive transfusion of fluids, blood and its products and more inotropic support may have a negative impact on the patient outcome.

  9. Nurse–patient collaboration

    Sørensen, Dorthe; Frederiksen, Kirsten; Grøfte, Thorbjørn;

    2013-01-01

    Objectives: This paper provides a theoretical account of nurses’ collaboration with patients with chronic obstructive pulmonary disease during non-invasive ventilation treatment in hospital. Background: Despite strong evidence for the effect of non-invasive ventilation treatment, success remains a...... huge challenge. Nurse-patient collaboration may be vital for treatment tolerance and success. A better understanding of how nurses and patients collaborate during non-invasive ventilation may therefore contribute to improvement in treatment success. Design: A constant comparative classical grounded...... theory. Method: The data comprised sessions of qualitative participant observation during the treatment of 21 patients with non-invasive ventilation that included informal conversations with the nurses and semi-structured interviews with 11 patients after treatment completion. Data were collected at...

  10. Patient dosimetry in hysterosalpingography

    The objectives of this study were to determine the entrance surface dose to the patient and to estimate the dose to the uterus and ovaries due to hysterosalpingography (HSG) diagnostic examinations performed in Recife-Pe, Brazil. The entrance doses were measured using four thermoluminescent dosimeters per patient, attached to anatomical landmarks on the patient's skin. The study was carried out on 25 patients between 21 and 45 years of age who underwent the HSG examinations in two training hospitals and one private radiodiagnostic institute. The number of exposures performed ranged from 4 to 15 radiographs per patient measured. Entrance surface doses varied between 4.99 and 36.6 mGy, with an average of 12.6mGy. The doses to the ovaries and uterus ranged from 0.80 mGy to 5.8 mGy and 1.10mGy to 8.05 mGy, respectively. (author)

  11. Measuring improved patient choice.

    Holmes-Rovner, M; Rovner, D R

    2000-08-01

    Patient decision support (PDS) tools or decision aids have been developed as adjuncts to the clinical encounter. Their aim is to support evidence-based patient choice. Clinical trials of PDS tools have used an array of outcome measures to determine efficacy, including knowledge, satisfaction, health status and consistency between patient choice and values. This paper proposes that the correlation between 'subjective expected utility' (SEU) and decision may be the best primary endpoint for trials. SEU is a measure usually used in behavioural decision theory. The paper first describes how decision support tools may use decision analysis to structure the presentation of evidence and guide patient decision-making. Uses of expected utility (EU) are suggested for evaluating PDS tools when improving population health status is the objective. SEU is the theoretically better measure when internal consistency of patient choices is the objective. PMID:11083037

  12. IMPROVING PATIENT SAFETY:

    Bagger, Bettan; Taylor Kelly, Hélène; Hørdam, Britta

    2013-01-01

    Every year millions of patients worldwide suffer injury or death due to unsafe care, thus improving patient safety is both a national and international priority. A developmental project involving University College Zealand and clinical partners in the region focused upon the improvement of patient...... safety by optimizing the theory-practice connection with respect to the development of students’ competencies and the reporting of clinical errors. Population: 2nd year nursing students at University College Zealand (N: 56). Informed consent and full anonymity. Aims: - To increase patient safety by...... raising student awareness with respect to the role of the reporting of clinical errors and thus increase patient safety - To prepare a structured and systematical teaching program Methodology: an explorative, longitudinal study - Identification of students’ self-evaluated knowledge, skills and competences...

  13. Patient Delay in Colorectal Cancer Patients

    Pedersen, Anette Fischer; Hansen, Rikke P; Vedsted, Peter

    2013-01-01

    Blødning fra endetarmen ses normalt som et alarmsymptom på kolorektalkræft. Alligevel vælger mange patienter at lade være med at opsøge lægen. Denne artikel ser nærmere på sammenhængen mellem et alarmsymptom (rektal blødning), forsinkelser i patientforløbet og tanker om kræft. Resultaterne viser,...

  14. IMPROVING PATIENT SAFETY:

    Bagger, Bettan; Taylor Kelly, Hélène; Hørdam, Britta

    2013-01-01

    Improving patient safety is both a national and international priority as millions of patients Worldwide suffer injury or death every year due to unsafe care. University College Zealand employs innovative pedagogical approaches in educational design. Regional challenges related to geographic......, social and cultural factors have resulted in a greater emphasis upon digital technology. Attempts to improve patient safety by optimizing students’ competencies in relation to the reporting of clinical errors, has resulted in the development of an interdisciplinary e-learning concept. The program makes...

  15. Patient Dosimetry. Chapter 22

    Patient exposures arising from radiological procedures form the largest part of the population exposure from artificial sources of radiation. According to United Nations Scientific Committee on the Effects of Atomic Radiation, the annual frequency of X ray examinations is 360 per 1000 individuals worldwide. Owing to the associated risk of radiation detriment to the patient, there is a clear need to monitor and control these exposures, and to optimize the design and use of the X ray imaging equipment so that the patient dose is reduced as far as possible, consistent with achieving the required clinical image quality

  16. Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

    de Borja Callejas, Francisco; Martínez-Antón, Asunción; Alobid, Isam; Fuentes, Mireya; Cortijo, Julio; Picado, César

    2014-01-01

    Background Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model that could be useful both for studying the role of epithelium in CRSwNP while developing new therapeutic strategies, including cell therapy, for CRSwNP. PMID:24945146

  17. Immature teratoma of the nose and paranasal sinuses masquerading as bilateral nasal polyposis: A unique presentation

    Aggarwal, S. K.; A Keshri; P Agarwal

    2013-01-01

    Teratomas are tumors of multipotent cells derived from all three germ cell layers and recapitulate normal organogenesis. Teratomas are hypothesized to arise by misplacement of multipotent germ cells. Teratoma is usually developmental and sometimes congenital neoplasm which displays both solid and cystic components with gross and microscopic differentiation into a wide variety of tissues representative of all three germ layers-ectoderm, mesoderm and endoderm. We are describing a case which was...

  18. Juvenile polyposis of the stomach--a novel cause of hypergastrinemia

    Papay, Karen D; Falck, Vincent G; Poulsen, Steen Seier;

    2010-01-01

    A 38-year-old female presented with a 3-year history of postprandial abdominal pain, refractory nausea, vomiting and hematemesis. She appeared malnourished and her symptoms were refractory to previous treatment with acid-suppressive drugs, prokinetics and antiemetics. Her medical history was sign...

  19. A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice.

    Waaler, Jo; Machon, Ondrej; Tumova, Lucie; Dinh, Huyen; Korinek, Vladimir; Wilson, Steven Ray; Paulsen, Jan Erik; Pedersen, Nina Marie; Eide, Tor J; Machonova, Olga; Gradl, Dietmar; Voronkov, Andrey; von Kries, Jens Peter; Krauss, Stefan

    2012-06-01

    Increased nuclear accumulation of β-catenin, a mediator of canonical Wnt signaling, is found in numerous tumors and is frequently associated with tumor progression and metastasis. Inhibition of Wnt/β-catenin signaling therefore is an attractive strategy for anticancer drugs. In this study, we have identified a novel small molecule inhibitor of the β-catenin signaling pathway, JW55, that functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2), regulators of the β-catenin destruction complex. Inhibition of TNKS1/2 poly(ADP-ribosyl)ation activity by JW55 led to stabilization of AXIN2, a member of the β-catenin destruction complex, followed by increased degradation of β-catenin. In a dose-dependent manner, JW55 inhibited canonical Wnt signaling in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of β-catenin. In addition, JW55 reduced XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice. Together, our findings provide a novel chemotype for targeting canonical Wnt/β-catenin signaling through inhibiting the PARP domain of TNKS1/2. PMID:22440753

  20. Small Intestinal Tumours: An Overview on Classification, Diagnosis, and Treatment

    Chiara Notaristefano

    2014-12-01

    Full Text Available The small intestinal neoplasia group includes different types of lesions and are a relatively rare event, accounting for only 3-6% of all gastrointestinal (GI neoplasms and 1-3% of all GI malignancies. These lesions can be classified as epithelial and mesenchymal, either benign or malignant. Mesenchymal tumours include stromal tumours (GIST and other neoplasms that might arise from soft tissue throughout the rest of the body (lipomas, leiomyomas and leiomyosarcomas, fibromas, desmoid tumours, and schwannomas. Other lesions occurring in the small bowel are carcinoids, lymphomas, and melanomas. To date, carcinoids and GIST are reported as the most frequent malignant lesions occurring in the small bowel. Factors that predispose to the development of malignant lesions are different, and they may be hereditary (Peutz-Jeghers syndrome, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, neuroendocrine neoplasia Type 1, von Hippel-Lindau disease, and neurofibromatosis Type 1, acquired (sporadic colorectal cancer and small intestine adenomas, coeliac disease, Crohn’s disease, or environmental (diet, tobacco, and obesity. Small bowel tumours present with different and sometimes nonspecific symptoms, and a prompt diagnosis is not always so easily performed. Diagnostic tools, that may be both radiological and endoscopic, possess specificity and sensitivity, as well as different roles depending on the type of lesion. Treatment of these lesions may be different and, in recent years, new therapies have enabled an improvement in life expectancy.

  1. Analysis of radiation-induced small intestinal tumors in APCMin/+mice

    Effect of radiation on intestinal tumorigenesis was studied using APCMin/+ mouse, a hetero-knockout strain with highly tumorigenic sensitivity due to the lack of tumor suppressing adenomatous polyposis coli (APC) gene (the causing gene of human familial polyposis) (Min: multiple intestinal neoplasia). Offspring crossed by male APCMin/+ and female wild type c57BL/6N mice were used for experiments. Those offspring at the age of 2 weeks were irradiated by 2 Gy of 60Co-gamma ray at 1.22 Gy/min with the irradiator RE-1082 and were maintained thereafter for 9 and 19 weeks, when they were sacrificed for physical, hematological and histological examinations. No significant radiation-related changes were observed in wild type mice. In comparison with non-irradiated APCMin/+ mice, followings were observed with significance in irradiated animals: the peripheral hemoglobin value was decreased; spleen weight was increased; number of tumors present in small intestine increased to 2-fold; and a colorectal tumor as big as >2 mm diameter was observed in one mouse. Thus radiation promoted the intestinal tumor formation in APCMin/+ mice. (T.T.)

  2. Patient survey (HCAHPS) - National

    U.S. Department of Health & Human Services — The national average for the HCAHPS survey categories. HCAHPS is a national, standardized survey of hospital patients about their experiences during a recent...

  3. Acknowledging the back patient

    Damsgaard, Janne Brammer; Bastrup, Lene; Norlyk, Annelise; Birkelund, Regner

    and integrate findings of qualitative studies. Results: The analysis reveals that many back patients feel that their experiences and perceptions are ignored by the health professionals, who are often concerned about identifying the cause. This can result in patients feeling mistrusted, marginalised...... and reluctant to speak out. Therefore, telling about experiences and perceptions is important for back patients in order to feel accepted and acknowledged. The health professionals must incorporate the patients’ narratives as an integral part of the care and treatment. Conclusions: In order to...... acknowledge the back patient the narrative must be complemented by a different perspective that includes the issue of ethical responsibility. It is therefore also a question of adopting certain norms as binding; to be bound by obligation or loyalty. Thus, the literature review argues for a more process...

  4. Optimizing patient nutrition

    Geiker, Nina Rica Wium

    (Paper I). The present study is, to my knowledge, the only study investigating the validity of performed nutritional risk screenings by comparing them with medical records. Eight per cent of patients were correctly screened for nutritional risk. A total of 24% of 2393 patients were nutritionally screened......Malnutrition, under-nutrition and/or obesity, may develop due to disease but may also cause disease. The prevalence of under-nutrition among hospitalized patients is high: 40-60% are either already under-nourished on admittance or at-risk of becoming malnourished. As in the general population...... of prescription medication, and take longer to recover. Acknowledging the adverse effects of malnutrition on health, since 2006 it has been mandatory to screen all patients for nutritional risk within 24 hours of admittance at all hospitals in the Capital Region, Denmark. The compliance to and the validity...

  5. Patient survey (HCAHPS) - State

    U.S. Department of Health & Human Services — A list of the state averages for the HCAHPS survey responses. HCAHPS is a national, standardized survey of hospital patients about their experiences during a recent...

  6. Positioning devices for patients

    It has been suggested that it is very important to position patients reproducibly at different stages of radiotherapy treatment planning and treatment, or similar procedures. Devices have been described for positioning a patient's upper and lower thorax. This invention provides reproducible positioning for a female patient's breasts, for example in planning treatment of and treating breast tumours. The patient is placed prone, using for example an upper thorax device. A support device is placed central to and beneath her breasts to partially displace them outwards. The device may be triangular in section with one apex contacting the chest wall at the sternum. Restraining straps may be provided to hold the breasts against the support device. Means may be provided to take a healthy breast from the path of radiation through the tumour. (author)

  7. USU Patient Simulation Center

    Federal Laboratory Consortium — he National Capital Area (NCA) Medical Simulation Center is a state-of-the-art training facility located near the main USU campus. It uses simulated patients (i.e.,...

  8. Patient Treatment File (PTF)

    Department of Veterans Affairs — This database is part of the National Medical Information System (NMIS). The Patient Treatment File (PTF) contains a record for each inpatient care episode provided...

  9. Woe patient is purple

    Hatice Dogan

    2014-08-01

    Conclusion: Traumatic asphyxia is a clinical condition caused by blunt thoracoabdominal trauma, and with good trauma management patients can be discharged with less mortality and morbidity. [Cukurova Med J 2014; 39(4.000: 914-917

  10. Critically ill obstetric patients

    Kirti Rajesh Bendre; Tanvi Vijay Tuteja; Geeta Madhav Niyogi

    2015-01-01

    Background: Objectives: To review all obstetric patients admitted in Intensive Care Unit (ICU) to access ethiology, required interventions, maternal mortality and to identify the conditions associated with maternal death. Methods: This is a retrospective study carried out in a medical college with tertiary hospital facility in Mumbai. The ICU admissions for a period of 5 years from October 2005 to October 2010 were reviewed. Results: Over 5 years, 48 out of 10800 obstetric patients wer...

  11. Depression in dialysis patients.

    King-Wing Ma, Terry; Kam-Tao Li, Philip

    2016-08-01

    Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored ≥14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate-major depression. The treatment effect should be re-evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients. PMID:26860073

  12. [Patient safety: Glossary].

    Sabio Paz, Verónica; Panattieri, Néstor D; Cristina Godio, Farmacéutica; Ratto, María E; Arpí, Lucrecia; Dackiewicz, Nora

    2015-10-01

    Patient safety and quality of care has become a challenge for health systems. Health care is an increasingly complex and risky activity, as it represents a combination of human, technological and organizational processes. It is necessary, therefore, to take effective actions to reduce the adverse events and mitigate its impact. This glossary is a local adaptation of key terms and concepts from the international bibliographic sources. The aim is providing a common language for assessing patient safety processes and compare them. PMID:26294153

  13. Depression in hemodialysis patients

    To measure the frequency of depression and its risk factors in patients under going hemodialysis. It is a cross-sectional prospective study conducted at Hemodialysis unit of Shalamar Hospital and Shaikh Zayed Hospital, Lahore from 1/sup st/ January 2006 to 30/sup th/ April 2006. All patients getting regular hemodialysis for more than three months were included. Beck's Depression Inventory- II (BDI-II; adapted in Urdu) was administered on all the patients who were able to read or understand it. Blood sample were drawn at the same time for routine hematological, biochemical parameters and viral markers (Anti HCV and HbsAg). Diagnosis was made as per Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV) for correlation of psychological variables with clinical, hematological and biochemical parameters. Eighty nine patients were enrolled which included fifty two (58.4%) were male and seventy seven (86.5%) were married. Major causes of renal failure were diabetes, hypertension and chronic glomerulonephrotis. Duration of dialysis was from 03 to 49 months with mean of 19.64 +- 11.7 months. Severity of depression was categorized in to mild, moderate and severe on the basis of BDI score. Majority of the patients fifty (56.1%) were moderately to severely depressed and there was no gender difference in the prevalence of depression. Majority of patients undergoing hemodialysis were depressed. Major risk factors for depression were marital status, illiteracy, number of children, socioeconomic factors, gender, hypertension and hypoalbuminemia. Patients with anemia, hyponatremia and hyperkalemia had suicidal tendency. Patients with hepatitis C and disturbed liver function have strong correlation with psychological parameters. (author)

  14. Patient Centered Telemedicine

    Wenner, Allen R.

    1995-01-01

    Instant Medical History®1 is an interrogation expert system that uses the patient to generate the initial portion of the electronic medical record. Prior to a decision about what type of medical intervention is required, the patient uses an interactive voice response telephone system to respond to branching questions based on the answer to the previous question. The responses are translated into medical terminology and presented to medical personnel who can quickly determine the level of enco...

  15. Sex Education for Patients

    Zitner, David

    1985-01-01

    Sex education evokes a wide variety of responses in the community and from teachers. Consequently, physicians have a responsibility to present sex education material in a factual, objective way. Many people are misinformed about sexual behavior. Physicians can help patients and the community by being aware of appropriate sex education for each age group. A curriculum for sex education, and opportunities to provide sex information for patients of different ages and stages in the lifecycle, are...

  16. Leptospirosis in elderly patients

    Galya Ivanova Gancheva

    2013-01-01

    Leptospirosis is a re-emerging zoonosis with broad clinical spectrum and high mortality in severe forms. The aim of this study was to analyze clinical manifestations, laboratory findings, epidemiological data, and management in elderly patients with leptospirosis. Toward that end, we performed a descriptive analysis of 15 leptospirosis elderly cases (age 60-78 years) treated at the Clinic of Infectious Diseases of University Hospital - Pleven (1976-2012). Patients were serologically confirmed...

  17. White coat, patient gown.

    Wellbery, Caroline; Chan, Melissa

    2014-12-01

    Much has been written about the symbolic function of the white coat: its implications of purity, its representation of authority and professionalism, and its role in consolidating a medical hierarchy. By contrast, the medical literature has paid almost no attention to the patient gown. In this article, we argue that in order to understand the full implications of the white coat in the doctor-patient relationship, we must also take into account patients' dress, and even undress. We explore contemporary artistic images of white coat and patient gown in order to reveal the power differential in the doctor-patient relationship. Artistic representations capture some of the cultural ambivalence surrounding the use of the white coat, which confers professional status on its wearer, while undermining his or her personal identity. At the other end of the sartorial spectrum, hospital gowns also strip wearers of their identity, but add to this an experience of vulnerability. Although compelling reasons for continuing to wear the white coat in circumscribed settings persist, physicians should be mindful of its hierarchical implications. Ample room remains for improving patients' privacy and dignity by updating the hospital gown. PMID:24687912

  18. Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers

    Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (β-CATENIN) gene itself. Recently in Wilms tumors, WTX (Wilms tumor gene on the X-chromosome) was discovered as another gene involved in the destruction of β-CATENIN. As the WTX-gene harbors a short T6-microsatellite in its N-terminal coding region, we hypothesized that frameshift-mutations might occur in MSI-H CRCs in the WTX gene, thus additionally contributing to the stabilization of β-CATENIN in human CRCs. DNA was extracted from 632 formalin-fixed, paraffin-embedded metastatic CRCs (UICCIV) and analyzed for MSI-H by investigating the stability of the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence capillary electrophoresis (FCE). Then, in the MSI-H cases, well described mutational hot spot regions from the APC-, AXIN2- and CTNNBI genes were analyzed for genomic alterations by didesoxy-sequencing while the WTX T6-microsatellite was analyzed by fragment analysis. Additionally, the PCR products of T5-repeats were subcloned and mutations were validated using didesoxy-sequencing. Furthermore, the KRAS and the BRAF proto-oncogenes were analyzed for the most common activating mutations applying pyro-sequencing. mRNA expression of WTX from MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated using reverse transcription (RT-) PCR and FCE. In our cohort of 632 metastatic CRCs (UICCIV) we identified 41 MSI-H cases (6.5%). Two of the 41 MSI-H cases (4.8%) displayed a frameshift mutation in the T6-repeat resulting in a T5 sequence. Only one case, a male patient, expressed the mutated WTX

  19. Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H colorectal cancers

    Scheel Silvio K

    2010-08-01

    Full Text Available Abstract Background Genetically, colorectal cancers (CRCs can be subdivided into tumors with chromosomal instability (CIN or microsatellite instability (MSI. In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli is affected in most cases, high grade MSI (MSI-H CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (β-CATENIN gene itself. Recently in Wilms tumors, WTX (Wilms tumor gene on the X-chromosome was discovered as another gene involved in the destruction of β-CATENIN. As the WTX-gene harbors a short T6-microsatellite in its N-terminal coding region, we hypothesized that frameshift-mutations might occur in MSI-H CRCs in the WTX gene, thus additionally contributing to the stabilization of β-CATENIN in human CRCs. Methods DNA was extracted from 632 formalin-fixed, paraffin-embedded metastatic CRCs (UICCIV and analyzed for MSI-H by investigating the stability of the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence capillary electrophoresis (FCE. Then, in the MSI-H cases, well described mutational hot spot regions from the APC-, AXIN2- and CTNNBI genes were analyzed for genomic alterations by didesoxy-sequencing while the WTX T6-microsatellite was analyzed by fragment analysis. Additionally, the PCR products of T5-repeats were subcloned and mutations were validated using didesoxy-sequencing. Furthermore, the KRAS and the BRAF proto-oncogenes were analyzed for the most common activating mutations applying pyro-sequencing. mRNA expression of WTX from MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated using reverse transcription (RT- PCR and FCE. Results In our cohort of 632 metastatic CRCs (UICCIV we identified 41 MSI-H cases (6.5%. Two of the 41 MSI-H cases (4.8% displayed a frameshift mutation in the T6-repeat resulting in a T5 sequence. Only one case, a

  20. Glaucoma in patients with uveitis.

    Panek, W C; Holland, G N; Lee, D A; Christensen, R E

    1990-01-01

    The records of 100 patients (161 eyes) with uveitis were reviewed retrospectively to determine the prevalence of increased intraocular pressure, the forms of uveitis most commonly associated with glaucoma, and the forms that require specific glaucoma therapy. Secondary glaucoma was present in 23 patients (31 eyes): three of 24 patients with acute uveitis (three eyes, 12% of acute uveitis patients) and 20 of 76 patients with chronic uveitis (28 eyes, 26% of chronic uveitis patients). Eighteen ...