Search PubMed⌕ Search

Biomedical subjects

G Möslein

Publications and source records attributed to G Möslein.

At least 19 recordsLinked to original sources
PubMed2005

[Comparison of different stool tests for the detection of cancer of the colon].

BACKGROUND AND OBJECTIVE: Colonoscopy is the gold standard for the diagnosis of colonic neoplasia. Because of the low compliance, the discomfort of bowel preparation and the procedure itself and the (albeit small) risk of perforation or bleeding alternative procedures such as stool tests are being focused on. PATIENTS AND METHODS: After informed consent stool samples of 116 patients (44 male, 72 female, median age 47 years), scheduled for colonoscopy and 22 patients (17 m, 5 f, 69 y) with known colorectal cancer stool samples were collected. The samples were investigated by three methods: a biochemical (Guajak) test for fecal occult blood, an immunological test for fecal occult blood and a test determining the dimer pyruvat kinase M2 (tumor M2-PK). RESULTS: Sensitivity for detection of colorectal cancer or polyps was 27 % and 10 % for the biochemical test, 91 % and 19 % for the immunological test and 77 % and 48 % for the M2-PK-test, respectively. Specificity was 89 %, 94 % and 72 %, respectively. CONCLUSIONS: Both methods for detection of occult blood had a similar specificity. The sensitivity of the immunological test for the detection of colorectal cancer was significantly higher. The M2-PK-test had a markedly lower specificity in diagnosing cancer. Because of the low sensitivity for polyps the usefulness of stool tests is questionable. Reducing incidence and mortality of colorectal cancer should be achieved by colonoscopy, a recommendation that requires specific communication to the public.

Aged↗
PubMed2001

[Hereditary nonpolyposis colorectal carcinoma (HNPCC): surgical aspects].

1-5% of all patients presenting with colorectal cancer, have an underlying genetic predisposition with an autosomal dominant of pattern of inheritance. Recently the underlying molecular genetic pathway of this syndrome known as HNPCC (hereditary nonpolyposis colorectal cancer) has been characterized: the predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair genes. Colorectal cancers are the leading characterisitic of the syndrom and are frequently encountered at a young age of onset. However, endometrial cancer, stomach cancer, small bowel cancer, urinary tract cancer and skin cancer among others are also inherent to the syndrome. Based on the identification of the underlying molecular genetic pathway, predictive testing has become an option. Once the family-specific underlying pathogenic mutation in one of the DNA mismatch-repair genes has been identified in a proband, at-risk family members may be offered DNA testing with an unequivocal answer to if or if not they have inherited the increased cancer susceptibility. Multiple facets of family DNA testing require a multidisciplinary approach integrating clinicians, geneticists, psychologists, molecular biologist and pathologists. Mutations are identified in a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The incidence of recta cancer in HNPCC has as yet not clearly been defined, due to a lack of unequivocal data. In a retrospective analysis (submitted) rectal cancers were encountered in 30% of the HNPCC patients. Half of the patients affected developed metachronous colon cancers. It is essential to address the issue of prophylactic surgery in HNPCC patients presenting with colorectal cancer: Prospective data is required in order to decide which of the options is more beneficial for the HNPCC patient presenting with his first colorectal primary: subtotal colectomy and ileorectal anastomosis versus restorative proctocolectomy. It is evident that apart from the more clinical data quality of life data must be evaluated in this study.

Colectomy↗
PubMed2001

The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)--results of an international collaborative study.

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal dominant condition accounting for 2-5% of all colorectal carcinomas as well as a small subset of endometrial, upper urinary tract and other gastrointestinal cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which account for most HNPCC cancers, are commercially available. This study sought to investigate the potential utility of these antibodies in determining the expression status of these proteins in paraffin-embedded formalin-fixed tissue and to identify key technical protocol components associated with successful staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2 mutation and expression status underwent immunoperoxidase staining at multiple institutions, each of which used their own technical protocol. Staining for hMSH2 was successful in most laboratories while staining for hMLH1 proved problematic in multiple labs. However, a significant minority of laboratories demonstrated excellent results including high discriminatory power with both monoclonal antibodies. These laboratories appropriately identified hMLH1 or hMSH2 inactivation with high sensitivity and specificity. The key protocol point associated with successful staining was an antigen retrieval step involving heat treatment and either EDTA or citrate buffer. This study demonstrates the potential utility of immunohistochemistry in detecting HNPCC probands and identifies key technical components for successful staining.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Prediction of the outcome of genetic testing in HNPCC kindreds using the revised Amsterdam criteria and immunohistochemistry.

BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) may be caused by mutations in the mismatch repair (MMR) genes MLH1, MSH2 or MSH6. Family history (Amsterdam criteria) has traditionally been used to select patients for mutation testing. It has been demonstrated that germline mutations in the MMR genes are associated with lack of the corresponding gene product as assessed with immunohistochemistry (IHC) in tumour specimens. The aim of the study was to assess the value of the Amsterdam criteria II and IHC in predicting germline mutations. METHODS: Fifty-six families that were previously tested for MLH1, MSH2 and MSH6 mutations were selected for this study. All pedigrees were extended and verified and the families were scored according to the original (I) and the revised Amsterdam criteria (II). The probabilities for MLH1 and MSH2 mutations were calculated by logistic regression. In addition, all available tumour material from indexed family members was examined by IHC for the presence of the three gene products. RESULTS: Three out of seven (39%) families where the mutation could be identified complied with the Amsterdam criteria I, while all seven (100%) met the Amsterdam criteria II. All families carrying a MLH1 or MSH2 mutation had > 15% calculated probability of finding a mutation. Tumours from all seven mutation carriers lacked the immunohistochemical expression of the corresponding MMR gene. CONCLUSION: The results indicate that the Amsterdam criteria II in combination with immunohistochemistry of the mismatch repair proteins in tumours may be a cost-effective approach to select families for mutation analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families.

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 the APC 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 carrying APC 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 Coli↗
PubMed2001

[Preventive therapy of HNPCC--a study concept].

Due to different pattern of penetrance and heterogeneity, the role of prophylactic surgery must be individually defined for every hereditary cancer predisposition. For HNPCC (hereditary nonpolyposis colorectal cancer) subtotal colectomy at the time of colorectal cancer diagnosis is being recommended by the Cancer Genetics Studies Consortium Recent Guidelines from the DGVS (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) state that to date no general recommendation favouring this approach can be made. The open question is: how effective is segmental resection and endoscopic surveillance in given time intervals compared with the reduction of risk by performing extended (prophylactic) surgery. Also the issue of dealing with rectal cancer as the first primary in HNPCC patients must be addressed. In order to answer these questions and after the lessons learned from BRCA mutation carriers and prophylactic mastectomies, quality of life measurement is mandatory for this study.

Colectomy↗
PubMed2000

[The desmoid problem].

Desmoid tumors (DTs) are rare nonmetastasizing neoplasms, occurring both sporadically and in the context of familial adenomatous polyposis (FAP). DTs show an unpredictable natural course with approximately 10% demonstrating a severely aggressive growth pattern, whereas others regress spontaneously. Surgery appears to have a triggering effect on desmoid growth, but is unavoidable in patients with FAP requiring prophylactic colectomy. Treatment recommendations remain controversial. Surgery may only be regarded as an option if a safety margin of at least 2 cm is guaranteed. Even under these circumstances recurrence rates are very high. Debulking operations invariably lead to a boost towards more aggressive growth. Most issues regarding DTs are contradictory, reflecting the lack of any systematic approach to the disease. One way out of this dilemma is the establishment of a clinical classification as a first step towards standardized therapy.

Adenomatous Polyposis Coli↗
PubMed2000

Extraintestinal polyps in Peutz-Jeghers syndrome: presentation of four cases and review of the literature. Deutsche Peutz-Jeghers-Studiengruppe.

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by hamartomatous polyps in the gastrointestinal tract and typical pigment lesions. Extraintestinal polyps have rarely been reported. Possible sites include the respiratory tract, urogenital tract, and gallbladder. We here describe four cases of extraintestinal polyps in PJS patients and review the literature on the need for operative therapy of extraintestinal polyps in PJS. Three nonrelated patients were examined who had PJS and polyps in the gallbladder; the fourth patient had PJS and recurrent choanal polyps. Surgery has so far been performed only for symptomatic polyps: one laparoscopic cholecystectomy and removal of the choanal polyps for recurrent infections of the respiratory tract. The remaining two patients reported no symptoms from the extraintestinal polyps. No malignant transformation was found in these patients, nor has such been reported in the literature on PJS. The frequent observation of this manifestation in our patients raises the question of clinical management: Is prophylactic surgery indicated? Since malignant transformation of PJS polyps in the intestine is extremely rare we see no reason for operative therapy as long as the polyps are small and asymptomatic. Regular sonographic controls are recommended since the risk of malignant transformation cannot be ruled out at present.

Adult↗
PubMed1998

Management of desmoid tumors in patients after ileal pouch-anal anastomosis for familial adenomatous polyposis.

PURPOSE: The aim of this study was to review the management of desmoid tumors in patients who have undergone ileal pouch-anal anastomosis for familial adenomatous polyposis and their outcome. METHODS: A retrospective review of case notes was undertaken in a series of 196 patients with familial adenomatous polyposis who had had an ileal pouch-anal anastomosis. Eleven patients were identified in whom desmoid tumor had developed (4 male; median age, 30 (range, 16-43) years). RESULTS: Desmoid tumors developed in the abdominal wall alone in 4 of 11 patients. Three enlarging tumors were resected with no subsequent recurrence. No patient received adjuvant treatment and pouch function remained stable at a median follow-up of eight years. Mesenteric desmoid tumors developed in seven patients; the pouch has been excised in two because of ischemia; two other patients have had defunctioning stomas created because of slow progression of their desmoid tumors. One patient had a single-lumen pouch excised and a new S-pouch inserted, with no subsequent recurrence of the desmoid tumor, and in two patients the mesenteric desmoid tumor has remained unchanged. All of these patients received long-term Clinoril (sulindac, Merck & Co., Inc., West Point, PA). Although there has been no significant deterioration in pouch function in patients in whom the pouch remains in situ, the pouch function was significantly worse compared with a control group of patients after ileal pouch-anal anastomosis for familial adenomatous polyposis in whom desmoid tumors did not develop. CONCLUSION: Desmoid tumors developed in 5.6 percent of 196 patients after ileal pouch-anal anastomosis for familial adenomatous polyposis. No patient with abdominal-wall desmoid tumor had a recurrence after local excision. By contrast, mesenteric desmoid tumors eventually resulted in pouch failure in four of seven affected patients.

Abdominal Muscles↗
PubMed1998

[Protein expression of hMSH2 and hMLH1 in HNPCC: evaluation of a prescreening method].

We show that immunohistochemistry for hMSH2 and hMLH1 is an easy and reproducible routine procedure. The interpretation of the staining results is unequivocal and investigator-independent. It is now necessary to validate the specificity and sensitivity of the method in a multicenter study with tumors of known mutations. As a consequence perhaps MIN testing may be replaced by immunohistochemistry as a first-line pretesting for HNPCC, reducing cost and time required.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[Rectal carcinomas in HNPCC].

The true incidence of rectal cancer in HNPCC is still unknown. In our retrospective series analyzing 42 probands from HNPCC families, we found rectal cancer primaries in 29% of our probands. Patients with a first cancer diagnosed in the rectum developed metachronous colon cancer in 54% of the cases. These numbers indicate a requirement to discuss the most appropriate surgical procedure for preventive intervention (ileorectal anastomosis versus ileoanal pouch procedure).

Adult↗
PubMed1995

Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444.

An earlier study has shown that FAP patients with mutations in codons 136-302 of the APC gene do not develop congenital hypertrophy of the retinal pigment epithelium (CHRPE), whereas those with mutations in codons 463-1387 regularly do. Here we present data on 36 patients from 20 families with mutations in codons 1445-1578. These patients lack CHRPE. Furthermore, with the exception of three prepubertal children all patients with mutations in codons 1445-1578 developed desmoid tumours. This relationship between certain extracolonic manifestations and site of the APC mutation points to a specific role of the APC protein in different tissues.

Adenomatous Polyposis Coli↗
PubMed1995

[Restorative proctocolectomy with ileoanal J-pouch in symptomatic children with familial adenomatous polyposis coli (FAP). Indications and results].

Familial adenomatous polyposis (FAP) is a genetic disorder leading to the early development of numerous polyps of the entire colorectum. First polyps usually emerge in puberty and cause symptoms in the third and fourth decade of life when a malignant transformation of the adenomas via an adenoma-carcinoma-sequence has often already occurred. Extracolonic manifestations and age of onset of the disease show a wide range of variability rendering the establishment of unequivocal standards for the timing of diagnostic, prophylactic and therapeutic modalities difficult. We report the cases of two unrelated children who presented with severe symptomatic, pancolonic polyposis already at the age of 3. Molecular diagnostics revealed a 'new mutation' in one case, the other child had a family history for FAP. Rapid progression of the disease with anemia and slight growth retardation were the indications for prophylactic surgery at the age of 7. The operative procedure performed was restorative proctocolectomy followed by an ileal pouch-anal anastomosis. Both children developed small bowel adhesions that forced us to perform an early closure of the protective ileostomy 3 weeks postoperatively. The subsequent course was uneventful. The children are now thriving and lead a normal social life. After only 3 months their stool frequency ranged between 2 and 5 times daily.

Adenomatous Polyposis Coli↗