90 research outputs found
Descriptive epidemiology of small intestinal malignancies: the German Cancer Registry experience
Progression of duodenal adenomatosis in familial adenomatous polyposis: due to ageing of subjects and advances in technology
Familial adenomatous polyposis patients are at risk of duodenal cancer. Surveillance is indicated and the extent of duodenal polyposis is quantified by the Spigelman staging system. We noticed an impressive increase in high Spigelman stages over the years and therefore decided to investigate whether this increase might be due to the time-lapse since the inception of surveillance or related to improvements in endoscopic imaging and/or changes in dysplasia-reporting. Patients who were investigated by the same endoscopist since 1980 in at least 2 different episodes of technical improvements were eligible. The period 1980–2009 was divided into 4 episodes using the following landmarks: replacement of fibre-endoscopes by video-endoscopes in 1987, change in processors in 1995, change in image resolution in 2000, and change in dysplasia-reporting in 2006. An increase in Spigelman stages from low stages (0–II 100%) to high stages (III 28.1%, IV 43.8%) was seen (median follow-up: 19.5 years). In patients who progressed, a median of 4 years elapsed before progression by one stage occurred and 7 years to progress by two stages. In a mixed-model analysis, both time-lapse and technical improvements were determinant factors for duodenal disease progression. When both factors were introduced in the model, the time-lapse as well as the change in image resolution and dysplasia-ranking contributed consistently in increasing Spigelman scores and stages. The impressive increase in severity of duodenal polyposis is determined by time-lapse, technological advances and change in dysplasia-reporting. These results might call for a revised Spigelman classification
Mutations in STK11 gene in Czech Peutz-Jeghers patients
<p>Abstract</p> <p>Background</p> <p>Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. The germline mutations in the serine/threonine kinase 11 (<it>STK11</it>) gene have been shown to be associated with the disease. Individuals with PJS are at increased risk for development of various neoplasms. The aim of the present study was to characterize the genotype and phenotype of Czech patients with PJS.</p> <p>Methods</p> <p>We examined genomic DNA of 8 individuals from five Czech families by sequencing analysis of <it>STK11 </it>gene, covering its promotor region, the entire coding region and the splice-site boundaries, and by multiplex ligation-dependent probe amplification (MLPA) assay designed for the identification of large exonic deletions or duplications of <it>STK11 </it>gene.</p> <p>Results</p> <p>We found pathogenic mutations in <it>STK11 </it>gene in two families fulfilling the diagnostic criteria of PJS and in one of three sporadic cases not complying with the criteria. The patient with the frameshift mutation in <it>STK11 </it>gene developed aggressive gastric cancer. No other studied proband has developed a carcinoma so far.</p> <p>Conclusion</p> <p>Our results showed that a germline mutation of <it>STK11 </it>gene can be found not only in probands fulfilling the PJS diagnostic criteria, but also in some sporadic cases not complying with the criteria. Moreover, we observed a new case of aggressive gastric cancer in a young patient with a frameshift mutation of <it>STK11 </it>gene.</p
Gastric adenomas in familial adenomatous polyposis are common, but subtle, and have a benign course
Familial adenomatous polyposis
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 suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program
A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome
Clinical governance: A review of key concepts in the literature
Purpose - This paper aims to explore the development of the concept of clinical governance as an international approach to addressing quality and safety issues in healthcare. Design/methodology/approach - The authors reviewed and analysed published clinical governance abstracts from 1966 to 2009. Citations were identified through a systematic search of Medline, Embase and CINAHL databases. A time series analysis was undertaken on the citations. The contents of the abstracts were then examined using an automated data-mining software package in order to identify underlying concepts. Findings - A total of 2,000 publications which made direct mention of clinical governance were identified across the 43-year search period. All were produced after 1998. This was when the concept was first seriously mobilised. Of the 2,000 citations, 2.3 per cent were published in 1998 and 6.3 per cent in 2008 (the last complete year available). The peak was reached in 2003, when 12.7 per cent of all clinical governance citations were published. The years 1998 to 2003 accounted for 59.2 per cent of all citations (to September 2009). There has been a steady decrease in the number of citations making direct reference to clinical governance since 2003. Originality/value - This paper maps the development and peak of clinical governance as a mobilising concept in healthcare in the late twentieth and early twenty-first centuries and shows how its conceptual underpinnings have been taken up by wider quality and safety agendas. Fads and fashions rise and fall in healthcare, as in other areas of life. © 2011 Emerald Group Publishing Limited
Patient safety teaching in Australian medical schools: A national survey
Objective To measure perceptions of Australian medical students and staff about whether key Learning Topics included in the National Patient Safety Education Framework (NPSEF) are being taught and what challenges to patient safety teaching are thought to be operating. Methods A cross-sectional survey of medical deans, educators and students was conducted in 2010. Twenty of twenty-one Australian medical schools participated. Using a five-point Likert scale, respondents rated whether patient safety topics were taught in their medical school and challenges to including patient safety in the curriculum. Results There were 2413 eligible responses: deans (or nominees) (n = 14); medical educators (n = 98); and medical students (n = 2301). There was most agreement that teaching occurred about communicating effectively (8% neutral or disagreed) and least agreement that there was teaching about adverse events and near misses (35% neutral or disagreed). Deans, educators and students responded positively about available champions and expertise and negatively to the curriculum being too full to include patient safety. There were consistent differences between the responses of the stakeholder groups (P < 0.0005 in a non-parametric test). Deans were more positive than educators, who were more positive than students. Conclusions Strong variability between perceptions of Learning Areas reveals opportunities for improvement in teaching about patient safety, especially in the area of recognizing and addressing adverse events and risks. Consistent differences across stakeholder groups reveal disparities in the perceptions of the teachers and their students. The results indicate targets for improving patient safety learning and closing the feedback loop between students and staff
Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer
Background: Lynch syndrome is caused by germline mutations in the mismatch repair genes and is characterised by a familial accumulation of colorectal and other cancers. Earlier identification of Lynch syndrome patients enables surveillance and might reduce the risk of cancer. It is important to explore whether today’s clinical care discovers patients with Lynch syndrome suitable for surveillance in time. This study aimed to describe what led to a diagnosis of Lynch syndrome in the cohort referred to the Hereditary Gastrointestinal Cancer Unit, Karolinska University Hospital, Solna, Sweden for gastrointestinal surveillance. Methods: This was a descriptive study. Data from 1975 to 2018 were collected and compiled as a database. Age at diagnosis was calculated from the date when a pathogenic MMR gene mutation was confirmed, from the period June 1994–September 2018. Data were collected from patient protocols prospectively during patient consultations and medical records retrospectively. Criteria for inclusion were registration at the outpatient clinic and a confirmed mismatch repair gene mutation. Results: A total of 305 patients were eligible for inclusion. Three major reasons for diagnosis were identified: 1. Predictive testing of a previously known mutation in the family (62%, mean age 37), 2. A family history of Lynch associated tumours (9%, mean age 37), 3. A diagnosis of cancer (29%, mean age 51). The proportion diagnosed due to cancer has not changed over time. Conclusion: A high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer, which suggests that there is significant room for improvement in the diagnosis of patients with Lynch syndrome before cancer develops
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