Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the ...effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged.
The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds.
Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided.
The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UPUK
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 with presumed AFAP, defined as having ≤100 colorectal adenomas at age ≥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‐two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5′ end, exon 9 and 3′ end).
Conclusions A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and <100 colorectal adenomas at age 25 or older. Colonoscopy had to be preferred to sigmoidoscopy and surveillance had to be life‐long. In the majority of patients, prophylactic colectomy and ileorectal anastomosis are recommended at the age of 20–25 years.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND AND AIMS In familial adenomatous polyposis (FAP), correlations between site of mutation in the adenomatous polyposis coli (APC) gene and severity of colonic polyposis or extracolonic ...manifestations are well known. While mutation analysis is important for predictive diagnosis in persons at risk, its relevance for clinical management of individual patients is open to question. METHODS We examined 680 unrelated FAP families for germline mutations in theAPC gene. Clinical information was obtained from 1256 patients. RESULTS APC mutations were detected in 48% (327/680) of families. Age at diagnosis of FAP based on bowel symptoms and age at diagnosis of colorectal cancer in untreated patients were used as indicators of the severity of the natural course of the disease. A germline mutation was detected in 230 of 404 patients who were diagnosed after onset of bowel symptoms (rectal bleeding, abdominal pain, diarrhoea). When these patients were grouped according to the different sites of mutations, mean values for age at onset of disease differed significantly: patients carryingAPC mutations at codon 1309 showed a disease onset 10 years earlier (mean age 20 years) compared with patients with mutations between codons 168 and 1580 (except codon 1309) (mean age 30 years), whereas patients with mutations at the 5′ end of codon 168 or the 3′ end of codon 1580 were diagnosed at a mean age of 52 years. Within each group of patients however large phenotypic variation was observed, even among patients with identical germline mutations. A higher incidence of desmoids was found in patients with mutations between codons 1445 and 1580 compared with mutations at other sites, while no correlation between site of mutation and presence of duodenal adenomas was observed. CONCLUSIONS As age at manifestation and course of the disease may be rather variable, even in carriers of identical germline mutations, therapeutic decisions should be based on colonoscopic findings in individual patients rather than on the site of mutation. However, in patients with mutations within codons 1445–1580, it may be advisable to postpone elective colectomy because desmoids may arise through surgical intervention.
Adenomatous polyposis (AP) diseases, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MUTYH‐associated polyposis (MAP), are the second most common hereditary causes of ...colorectal cancer. A frequent extra‐colonic manifestation of AP disease is duodenal polyposis, which may lead to duodenal cancer in up to 18% of AP patients. Endoscopic surveillance is recommended at 0.5‐ to 5‐year intervals depending on the extent of polyp growth and histological progression. Although the Spigelman classification is traditionally used to determine surveillance intervals, it lacks information on the (peri‐)ampullary site, where 50% of duodenal carcinomas are located. Hence, information on the papilla has recently been added as a prognostic marker. Patients with duodenal adenoma(s) ≥10 mm and ampullary adenomas of any size are suggested to be referred to an expert center for endoscopic therapy, particularly endoscopic mucosal resection and endoscopic ampullectomy. Nonetheless, despite the logic of this approach, the long‐term efficacy of endoscopic therapy is still to be demonstrated.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one ...of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.
Hereditary non-polyposis colorectal cancer (HNPCC) is a common autosomal dominant condition characterized by early onset colorectal cancer as well as other tumour types at different anatomical sites. ...HNPCC tumours often display a high level of genomic instability, characterized by changes in repeat numbers of simple repetitive sequences (microsatellite instability, MSI), which reflects the malfunction of the DNA mismatch repair machinery. Accordingly, HNPCC was shown to be caused by germline mutations in the DNA mismatch repair genes (MMR) MSH2, MLH1, PMS1, PMS2 and MSH6. So far, more than 220 predisposing mutations have been identified, most in MSH2 and MLH1 and in families complying with the clinical Amsterdam criteria (AMS+). Many HNPCC famlilies, however, do not fully comply with these criteria, and in most cases the causative mutations are unknown.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Zusammenfassung
Hintergrund
Nachdem das Krebsfrüherkennungs- und Krebsregistergesetz (KFRG) im April 2013 als Rahmengesetz auf Bundesebene verabschiedet wurde, muss nun eine Ausgestaltung auf ...Länderebene folgen.
Fragestellung
Der Prozess ist eingeleitet: Festgelegt worden sind die allgemeinen Ziele, Zuständigkeiten, die Verantwortlichkeiten für die bundeseinheitlichen Datensätze sowie die Rahmenbedingungen für die Finanzierung der zukünftigen klinischen Krebsregister.
Material und Methoden
Das Gesetz verzichtet auf eine konkrete Formulierung von Qualitätsanforderungen, die an klinische Krebsregister zukünftig zu stellen sind. Diese müssen jetzt mit allen Beteiligten vereinbart werden. Ausschlaggebend war die Gründung einer Arbeitsgruppe zum Handlungsfeld 2 des Nationalen Krebsplans (NKP), das als „Ziel 8“ formuliert wurde.
Ergebnisse
Das Zielepapier dieser Arbeitsgruppe konkretisierte die Notwendigkeit zuverlässiger Qualitätsbewertungen, die die Umsetzung der leitliniengerechten Versorgung prüfen, ebenso den Nutzen und die Wirtschaftlichkeit innovativer Krebstherapien und die einen Vergleich der Leistungen messen, um Leistungsoptimierungen zu Gunsten der Krebspatienten zu erzielen.
Schlussfolgerungen
Die Entscheidung zu der Etablierung eines flächendeckenden Krebsregisters in Deutschland ist gefallen und die Weichen sind gestellt. Die Herausforderung besteht jetzt darin, eine Harmonisierung der heterogenen Landschaft auf Länderebene und bundesweit zu erreichen.
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