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1.
GMS J Med Educ ; 33(4): Doc54, 2016.
Article in English | MEDLINE | ID: mdl-27579354

ABSTRACT

The competent physical examination of patients and the safe and professional implementation of clinical procedures constitute essential components of medical practice in nearly all areas of medicine. The central objective of the projects "Heidelberg standard examination" and "Heidelberg standard procedures", which were initiated by students, was to establish uniform interdisciplinary standards for physical examination and clinical procedures, and to distribute them in coordination with all clinical disciplines at the Heidelberg University Hospital. The presented project report illuminates the background of the initiative and its methodological implementation. Moreover, it describes the multimedia documentation in the form of pocketbooks and a multimedia internet-based platform, as well as the integration into the curriculum. The project presentation aims to provide orientation and action guidelines to facilitate similar processes in other faculties.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Physical Examination , Faculty , Humans , Medicine
3.
Colorectal Dis ; 16(2): 116-22, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23941307

ABSTRACT

AIM: Restorative proctocolectomy with ileal pouch-anal anastomosis for patients with familial adenomatous polyposis (FAP) and ulcerative colitis (UC) has been modified from a transanal hand-suture after mucosectomy to a stapled ileal pouch-anal anastomosis (IPAA) without mucosectomy. Better functional results favour stapled anastomosis; however, stapled anastomosis results in higher rates of adenomas in persisting anorectal mucosa. The purpose of this study was to compare the two techniques of pouch-anal anastomosis with respect to early postoperative complications in a collective of FAP patients. METHOD: The study was performed as a matched-pair analysis. Data were obtained from a prospectively collected database. RESULTS: The overall rate of postoperative complications was higher after stapled IPAA (31% stapled vs 23% handsewn), with anastomotic stricture occurring in 24.3% (stapled) and 16.2% (handsewn) (P = 0.22). Any leakage or pelvic abscess formation after stapled anastomosis occurred within 30 days in almost all patients, whereas these were mainly diagnosed between 30 days and 6 months after handsewn IPAA. A laparoscopic approach was used in 56.7% of patients in the stapled group but in only two patients in the handsewn group. Intra-operative blood loss was significantly higher in the handsewn group (mean ± SD: 699 ± 511 ml vs 369 ± 343 ml; P < 0.0001), as was the volume of blood transfused (mean ± SD: 205 ± 365 ml vs 8 ± 49 ml; P < 0.0001). Function did not differ between the groups. CONCLUSION: There was a nonstatistically significant tendency towards a higher rate of early postoperative complications after stapled IPAA. The timing of anastomotic leakage and abscess formation differed between the groups.


Subject(s)
Abscess , Adenomatous Polyposis Coli/surgery , Anastomosis, Surgical/methods , Anastomotic Leak , Postoperative Complications , Proctocolectomy, Restorative/methods , Surgical Stapling , Suture Techniques , Adolescent , Adult , Case-Control Studies , Child , Cohort Studies , Colonic Pouches , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
4.
Chirurg ; 84(10): 859-68, 2013 Oct.
Article in German | MEDLINE | ID: mdl-24042436

ABSTRACT

Competency-based frameworks rely on relevant professional competency rather than formal regulations. The transitional phase between final year undergraduate and common trunk postgraduate medical training is characterized by an increase of professional responsibility whereby previously acquired knowledge, skills and abilities have to be merged and applied to patients. Undergraduate and postgraduate training programs should ensure a successive transfer of responsibility for medical practice to final year students and young residents depending on individual competence. The concept of entrustable professional activities (EPA) represents a curricular concept based on concrete medical tasks which may be assigned to the responsibility of the trainee.


Subject(s)
Clinical Competence , Education, Medical, Graduate/methods , Education, Medical, Undergraduate/methods , General Surgery/education , Internship and Residency , Clinical Competence/legislation & jurisprudence , Curriculum , Delivery of Health Care/legislation & jurisprudence , Education, Medical, Graduate/legislation & jurisprudence , Education, Medical, Undergraduate/legislation & jurisprudence , General Surgery/legislation & jurisprudence , Germany , Humans , Internship and Residency/legislation & jurisprudence , Physician-Patient Relations , Specialty Boards
5.
Chirurg ; 84(10): 869-74, 2013 Oct.
Article in German | MEDLINE | ID: mdl-24018916

ABSTRACT

BACKGROUND: For competency-oriented teaching in surgery a comprehensive medical educational training and professionalization of clinical teachers is essential. The Surgical Working Group for Teaching has therefore set itself the task of developing an appropriate training concept. METHOD: In the first step the core group took stock of the most relevant educational barriers in the clinical environment. Taking into account these findings a trimodular course was devised that addressed both previous knowledge and different clinical functions of the faculty as well as modern concepts of competency-based academic teaching. RESULTS: The A course is designed for medical teaching of novices with a focus on collation of the medical history, clinical examination and teaching of practical skills. The B course is devised for experienced clinicians and should qualify them for competency-based teaching in complex educational scenarios, such as the operating room or ward rounds, while the C course is directed to a group of persons entrusted with the organization and administration of clinical teaching.


Subject(s)
Competency-Based Education/organization & administration , Curriculum , General Surgery/education , Models, Educational , Societies, Medical , Clinical Competence , Competency-Based Education/methods , Faculty, Medical , Germany , Humans
6.
Schmerz ; 27(5): 475-86, 2013 Sep.
Article in German | MEDLINE | ID: mdl-24022410

ABSTRACT

BACKGROUND: Pain medicine as an interdisciplinary, multifaceted field has not yet been assigned the status of a separate medical subject in the curriculum of medical schools in Germany. Pain medicine is often taught by anesthesiologists, neurologists, orthopedic or neurological surgeons either by assignment by the Dean's office or because of their own enthusiasm. In the near future pain medicine as an interdisciplinary course will be mandatory in undergraduate medical education. The authors were interested to investigate the needs and demands of both students and instructors from theoretical and clinical fields in order to develop a longitudinal pain medicine curriculum. METHODS: Based on Kern's curriculum development model, the opinions of students and instructors were investigated: quantitative items were analyzed using Student's t-test for independent variables and heterogenic variance and the content of free text answers was analyzed by forming subsets of similar or identical answers. A concise curriculum was developed. RESULTS: Students from advanced classes noted a bigger discrepancy between the needs formulated and what was actually offered as compared to younger students. Instructors from different theoretical and clinical specialties were unaware of the topics of colleagues from other departments. The analysis of written answers revealed a different understanding of the term pain medicine. CONCLUSION: At the Hannover Medical School, a standardized needs assessment helped to develop LoMoS, the longitudinal pain medicine curriculum, which may also serve as a model for other medical faculties. Students required more practical instruction and teachers were interested in improving networking and discussion among specialists.


Subject(s)
Education, Medical, Graduate , Goals , Medicine , Needs Assessment , Pain Management/psychology , Adult , Attitude of Health Personnel , Cooperative Behavior , Curriculum , Faculty, Medical , Female , Germany , Humans , Interdisciplinary Communication , Longitudinal Studies , Male , Models, Educational , Pain Management/methods , Students, Medical/psychology , Surveys and Questionnaires
7.
Chirurg ; 84(4): 277-85, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23494054

ABSTRACT

Competency-based medical education is a prerequisite to prepare students for the medical profession. A mandatory professional qualification framework is a milestone towards this aim. The National Competency-based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM) of the German Medical Faculty Association (MFT) and the German Medical Association will constitute a basis for a core curriculum of undergraduate medical training. The Surgical Working Group on Medical Education (CAL) of the German Association of Surgeons (DGCH) aims at formulating a competency-based catalogue of learning objectives for surgical undergraduate training to bridge the gap between the NKLM and the learning objectives of individual medical faculties. This is intended to enhance the prominence and visibility of the surgical discipline in the context of medical education. On the basis of different faculty catalogues of learning objectives, the catalogue of learning objectives of the German Association of Orthopedics and Orthopedic Surgery and the Swiss Catalogue of Learning Objectives representatives of all German Surgical Associations cooperated towards a structured selection process of learning objectives and the definition of levels and areas of competencies. After completion the catalogue of learning objectives will be available online on the webpage of the DGCH.


Subject(s)
Clinical Competence/standards , Competency-Based Education/standards , Education, Medical, Undergraduate/standards , General Surgery/education , Catalogs as Topic , Curriculum/standards , Faculty, Medical , Germany , Humans , Orthopedics/education , Societies, Medical
8.
Br J Surg ; 100(5): 694-703, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23334997

ABSTRACT

BACKGROUND: Familial adenomatous polyposis (FAP) is caused by mutations in the adenomatous polyposis coli (APC) gene. Desmoid tumours affect up to 26 per cent of patients and contribute significantly to death. This study aimed to assess the influence of sex and mutation site on desmoid tumour development and sex-specific genetic differences in patients with FAP with and without desmoid tumours. METHODS: Patients with FAP-associated desmoid tumours recorded in the Heidelberg Polyposis Register between 1991 and 2010 were identified. These patients were analysed with respect to clinical parameters and possible risk factors. RESULTS: Some 105 patients with FAP-associated desmoid tumours of a total of 585 patients with FAP were analysed. Male patients had a significantly greater number of desmoid tumours and a larger tumour mass, although tumours were more common in female patients. Desmoid tumours in male patients were located more often in the abdominal wall. Seventy-nine (75.2 per cent) of the 105 patients demonstrated a clear temporal association between a previous operation and subsequent desmoid tumour development; most of these patients were female. Mutation sites in male patients were limited to exons 5, 14 and 15, whereas female patients carried mutations along the entire coding region of the APC gene. Twenty-one per cent of patients with desmoid tumours carried mutations within the 'desmoid region', compared with only 4.1 per cent of the control group without desmoids. CONCLUSION: There are significant sex differences concerning desmoid tumour manifestation. Female patients appear to have a higher risk of desmoid tumour occurrence independent of the mutation site, whereas in male patients the mutation site seems to exert more influence.


Subject(s)
Adenomatous Polyposis Coli/genetics , Exons/genetics , Fibromatosis, Aggressive/genetics , Genes, APC/physiology , Mutation/genetics , Adenomatous Polyposis Coli/pathology , Adult , DNA Mutational Analysis , Female , Fibromatosis, Aggressive/pathology , Humans , Male , Postoperative Complications/genetics , Pregnancy , Pregnancy Complications, Neoplastic/genetics , Prospective Studies , Sex Factors
10.
Zentralbl Chir ; 137(2): 138-43, 2012 Apr.
Article in German | MEDLINE | ID: mdl-22495488

ABSTRACT

BACKGROUND: The quality of postgraduate training is an important motivating factor for the career decisions of young doctors and has an impact on the satisfaction of postgraduate trainees. In Germany, we still lack a postgraduate training programme in surgery that defines the competency profile at the time of certification. This article describes the development of a national modular competency-based core curriculum for postgraduate surgery training as well as first experience and evaluation data from the initial period of implementation. METHODS: The curriculum was developed in a group of highly motivated surgeons according to the "Kern-cycle", a conceptual framework for curriculum development in medicine, and includs considerations from the "CanMEDS"-competency framework for physicians. The curriculum follows a "blended learning" concept with modular attendance courses and associated preparatory online courses. The didactics follows the principles of adult learning and are characterised by learner-centred, self-directed learning processes in small groups with feedback. The initial implementation phase was accompanied by a detailed evaluation of the general concept as well as the quality of content and didactics of the attendance courses. RESULTS: Seven of the planned 12 attendance courses have been designed, 6 courses have been implemented2q1. Altogether 562 participants from hospitals of all levels of patient care took part in the attendance courses, some of them in several courses. The gender distribution was almost balanced with a slight female surplus. The majority of participants were supported by their clinics through exemption from clinical work or financial sponsoring. 80 % of the participants completed the evaluation of the attendance courses. The data show a high degree of participant satisfaction with the content and didactic concept of the courses, as well as with the surrounding conditions and the commitment of the trainers. CONCLUSIONS: The evaluation data on the attendance courses implemented reveal a high acceptance among participants concerning the overall concept of the modular postgraduate training programme as well as the support of the programme by surgeons responsible for postgraduate training.


Subject(s)
Clinical Competence , Competency-Based Education/trends , Education, Medical, Continuing/trends , Education, Medical, Graduate/trends , General Surgery/education , Adult , Certification , Computer-Assisted Instruction/trends , Curriculum , Female , Forecasting , Germany , Health Services Needs and Demand/trends , Humans , Male , Workforce
11.
Colorectal Dis ; 13(11): e358-65, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21801297

ABSTRACT

AIM: Favourable outcomes for health-related quality of life (HRQL) have been reported in patients with familial adenomatous polyposis (FAP) after restorative proctocolectomy and ileal pouch-anal anastomosis (RPC). However, less is known about patients' subjective experience and adjustment to postoperative impairment. Using a multidimensional psychometric assessment, we investigated patient-reported HRQL to determine the impact of the patient's subjective experience together with medical, functional and psychosocial factors on HRQL. METHOD: In this cross-sectional study, 116 FAP patients who had undergone RPC on average 8 years earlier completed standardized and study-specific questionnaires and participated in a personal interview. The impact of medical, functional and psychosocial factors on patients' HRQL was determined by regression analyses. RESULTS: When using a generic psychometric measure, FAP patients' overall HRQL was comparable with that of the general population. Impaired HRQL, however, was found in patients reporting poor pouch function in contrast to those reporting good or moderate functional outcome. Findings from a personalized interview also suggested that a good functional result does not necessarily translate into good HRQL. Personal resources predicted patients' physical and psychological well-being, whereas little variance of HRQL was explained by medical factors and function. CONCLUSION: Patients' HRQL is, to a substantial degree, the result of adjustment to the adverse impact of RPC. By using personal resources the majority of patients may achieve satisfactory HRQL levels even when bowel function is impaired. A multidimensional assessment that comprises medical, functional and psychosocial aspects is required to ascertain an adequate evaluation of FAP patients after RPC.


Subject(s)
Adaptation, Psychological , Adenomatous Polyposis Coli/psychology , Colonic Pouches/physiology , Proctocolectomy, Restorative/psychology , Quality of Life/psychology , Adenomatous Polyposis Coli/surgery , Adolescent , Adult , Age Factors , Analysis of Variance , Attitude , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Linear Models , Male , Middle Aged , Proctocolectomy, Restorative/adverse effects , Psychometrics , Self Concept , Sexual Dysfunction, Physiological/psychology , Social Support , Surveys and Questionnaires , Young Adult
12.
Article in German | MEDLINE | ID: mdl-19626281

ABSTRACT

Since 2005, German universities are free to select 60% of their freshmen according to their own admission processes. In 2008, selection of medical students in Germany was mainly based on grades achieved in final school examinations (Abiturnote). Further criteria were used in various combinations: some medical schools conducted interviews or tests, while others rewarded work experience, research awards, or cultural and social dedication. However, solely high school grades and some measures of ability show acceptable validity coefficients with regard to academic and professional success. Evidence for the prognostic validity of interviews and other noncognitive criteria cannot be regarded as sufficient. Recent studies conducted in Hamburg and Heidelberg attempt to validate selection criteria such as a test of natural sciences, final school examination grades, work experience, and voluntary work in the social sector. For the selection of medical students, we recommend the use of final school examination grades in combination with special written test results or, in the case of dentistry, a test of manual dexterity. Interviews might be beneficial to emphasize the importance of non-academic skills and to strengthen the ties of students to their faculty.


Subject(s)
Aptitude , Education, Dental , Education, Medical , School Admission Criteria , Achievement , Career Choice , Educational Measurement , Germany , Humans , Interviews as Topic
13.
J Gastrointest Surg ; 13(2): 261-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18791770

ABSTRACT

BACKGROUND: Restorative proctocolectomy followed by an ileoanal J-pouch procedure is the therapy of choice for patients with familial adenomatous polyposis and ulcerative colitis. After low anterior rectal resection, the authors have reported on a novel, less complex pouch configuration, a transverse coloplasty pouch. The aim of the present work was to apply this new design to the ileal pouch construction, to evaluate feasibility, and to measure functional results in comparison with the J-pouch and the straight ileoanal anastomosis using the pig as an animal model. METHODS: Twenty-three pigs underwent restorative proctocolectomy followed by reconstruction with straight ileoanal anastomosis (IAA; n = 5), J-pouch (n = 7), and a transverse ileal pouch (TIP; n = 11). Pigs were followed for 6 days postoperatively. Peristaltic function was assessed by manometry proximal to the pouch, in the reservoir, and at the level of the ileoanal anastomosis. Functional outcome was monitored by semiquantitative assessment of the general condition of the animals, postoperative feeding habits, and stool frequency and consistency. A Fourier analysis was performed in order to compare peristalsis in the ileal reservoirs. The reservoir volume was measured in situ by triple contrast computed tomography scan with 3D reconstruction. RESULTS: Seventeen animals survived for 1 week. There was no difference in the general condition or the feeding habits of the groups. A significant number of pigs with the TIP pouch (7/10) had semisolid or formed stools as opposed to liquid stools after J-pouch (6/6) and IAA (4/5; p = 0.01). TIP animals had a lower stool frequency (3.2 +/- 1.14 per day) on day 6 after the operation than pigs with J-pouch, 5.33 +/- 1,03, and IAA, 4.6 +/- 1.82 (p = 0.0036). The in situ volume of the pouches did not differ significantly. The Fourier analysis demonstrated a disruption of peristalsis by the J-pouch and the TIP reconstruction but not after IAA. CONCLUSION: The function of ileoanal reservoirs after proctocolectomy may result from the disruption of properistaltic waves after pouch formation. The mechanism of peristalsis disruption is independent of the in situ volume of the pouch.


Subject(s)
Colonic Pouches , Ileum/surgery , Proctocolectomy, Restorative/methods , Recovery of Function/physiology , Anastomosis, Surgical/methods , Animals , Defecation/physiology , Feasibility Studies , Female , Gastrointestinal Motility/physiology , Swine , Time Factors
14.
Fam Cancer ; 5(2): 195-9, 2006.
Article in English | MEDLINE | ID: mdl-16736291

ABSTRACT

Hereditary Non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by germline mutations in at least four genes encoding integral components of the cellular DNA mismatch repair (MMR) system. The spectrum of genetic alterations encompasses missense- and nonsense mutations, intronic mutations affecting splice donor or acceptor sites as well as small-scale deletions and insertions. We have identified a 'nonsense' mutation that activates a cryptic splice site generating an in frame deletion of the last 17 codons of exon1 of the hMLH1 gene causing HNPCC in a German family. We present a comprehensive genetic analysis of this family that demonstrates important aspects of HNPCC pathogenesis.


Subject(s)
Carrier Proteins/genetics , Codon, Nonsense , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Nuclear Proteins/genetics , RNA Splicing , Adaptor Proteins, Signal Transducing , Adult , Humans , Male , MutL Protein Homolog 1
15.
Chirurg ; 77(4): 352-9, 2006 Apr.
Article in German | MEDLINE | ID: mdl-16477431

ABSTRACT

BACKGROUND: The medical faculty of Heidelberg University implemented a new problem-based clinical curriculum (Heidelberg Curriculum Medicinale, or Heicumed) in 2001. The present study analyses the evaluation data of two student cohorts prior to the introduction of Heicumed. Its aim was to specify problems of the traditional training and to draw conclusions for implementation of a new curriculum. METHODS: The evaluation instrument was the Heidelberg Inventory for the Evaluation of Teaching (HILVE-I). The data were analysed calculating differences in the means between defined groups, with the 13 primary scales of the HILVE I-instrument as dependent variables. RESULTS: Teaching method and subject had no systematic influence on evaluation results. Thus, didactic lecture in orthopedic surgery achieved better results than small group tutorials, while the data on vascular and general surgery showed opposite results. Major factors for success were continuity and didactic training of lecturers and tutors. This is convincingly reflected by the results of the lecture course "Differential diagnosis in general surgery". The good evaluation data on small group tutorials resulted largely from the "participation" and "discussion" scales, which represent interactivity in learning. CONCLUSION: The results of the present study suggest the importance of two major pedagogic ideas: continuity and didactic training of lecturers and tutors. These principles were widely implemented in Heicumed and have contributed to the success of the new curriculum.


Subject(s)
Education, Medical, Undergraduate , General Surgery/education , Problem-Based Learning , Attitude of Health Personnel , Cohort Studies , Curriculum , Educational Measurement , Faculty, Medical , Germany , Humans , Program Evaluation , Schools, Medical , Specialties, Surgical/education
16.
Chirurg ; 76(12): 1125-34, 2005 Dec.
Article in German | MEDLINE | ID: mdl-16323029

ABSTRACT

Familial adenomatous polyposis coli (FAP) may not be considered a single disease entity with standardized guidelines for operative treatment. However, prophylactic colectomy after the manifestation of polyps but prior to the development of colorectal cancer is essential. The optimal timing of prophylactic surgery remains a clinical decision taken independently of mutation analysis. In case of the classic FAP phenotype, restorative proctocolectomy and ileal pouch-anal anastomosis is the procedure of choice. The development of reliable guidelines for attenuated FAP variants requires further evidence from clinical studies on surgical strategy and the advantages of prophylactic surgery over regular endoscopic screening with removal of polyps.


Subject(s)
Adenomatous Polyposis Coli/surgery , Colectomy , Colorectal Neoplasms/prevention & control , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/pathology , Adolescent , Adult , Aged , Child , Child, Preschool , Colonic Pouches , Female , Genotype , Humans , Male , Middle Aged , Phenotype , Proctocolectomy, Restorative , Time Factors
17.
Chirurg ; 76(3): 273-81, 2005 Mar.
Article in German | MEDLINE | ID: mdl-15668807

ABSTRACT

Even in pancreatic surgery, as in other organs, there is a tendency towards subtle organ-preserving techniques. Benign duodenal tumors which cannot be resected transduodenally or multiple dysplastic duodenal adenomas in patients with familial adenomatous polyposis (FAP) usually require partial pancreaticoduodenectomy. However, pancreas-preserving duodenectomy may represent a viable alternative. This technique allows for the resection of the entire duodenum without resection of the pancreatic head. Large duodenal adenomas, multiple adenomas with dysplasia in patients with FAP, and based on the literature extended duodenal injury after trauma may represent indications for this surgical technique. Compared with duodenopancreatectomy, this intervention can be performed with a comparably low morbidity and leads to good functional results. Beside the preservation of pancreatic parenchyma and the reduction of the number of anastomoses, this technique offers the advantage of uncomplicated endoscopic follow-up. In this article we describe the surgical technique of pancreas-preserving duodenectomy and our experience with this intervention.


Subject(s)
Adenoma/surgery , Adenomatous Polyposis Coli/surgery , Duodenal Neoplasms/surgery , Duodenum/surgery , Pancreaticoduodenectomy/methods , Adult , Ampulla of Vater/surgery , Anastomosis, Surgical/methods , Cystic Duct/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pancreatitis/etiology , Postoperative Complications/etiology , Treatment Outcome
18.
Dis Colon Rectum ; 44(9): 1281-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11584201

ABSTRACT

PURPOSE: The Bethesda guidelines were developed for selection of patients whose tumors should be tested for high microsatellite instability. This study examined the validity of the different Bethesda criteria in relation to microsatellite instability status to simplify their use in clinical practice. METHODS: A total of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer-associated cancers were registered on the basis of the Amsterdam criteria without age limitations (11 cases), multiple tumors (2 cases), the accumulation of colorectal cancer in the family (no first-degree relatives affected or the index patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13 cases), morphologic and histopathologic manifestations (right-sided colorectal cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria (92 cases). The microsatellite instability status of tumors was determined using the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high microsatellite instability tumors were identified in our hereditary nonpolyposis colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent (27/92) of the Bethesda-positive patients displayed high microsatellite instability compared with 6 percent of patients (4/72) not meeting these criteria (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different distribution of the microsatellite instability status when compared with those of the remaining patients registered (P < or = 0.001). These three criteria detected high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36), and 31 percent (21/67) of patients, respectively. When applying these criteria only, a cumulative detection rate of 77 percent of all (24/31) high microsatellite instability cases was found, thereby identifying 89 percent of high microsatellite instability tumors among the Bethesda-positive patients. Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline mutations and tumor-specific loss of protein expression. CONCLUSION: In our hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria showed the highest sensitivity to identify patients with high microsatellite instability tumors. However, for general medical practice outside academic centers, three criteria are reasonably accurate for adequate high microsatellite instability tumor selection.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/genetics , DNA Repair , Microsatellite Repeats/genetics , Patient Selection , Adult , Aged , Base Pair Mismatch , Female , Guideline Adherence , Humans , Immunohistochemistry , Male , Middle Aged , Polymerase Chain Reaction , Practice Guidelines as Topic , Sensitivity and Specificity
19.
Int J Colorectal Dis ; 16(2): 63-75, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11355321

ABSTRACT

Familial adenomatous polyposis coli (FAP) is an autosomal dominant genetic disorder caused by mutations of the APC gene on the long arm of chromosome 5. While multiple colorectal adenomas usually developing in early adolescence represent the most conspicuous phenotypic feature, the disease represents a generalized hyperproliferative disorder with various extracolonic manifestations. Duodenal cancer and desmoids are the leading causes of death in FAP patients after prophylactic colectomy. The prevalence of duodenal adenomatosis among FAP patients varies from 50% to greater than 90%, while only few patients (3-5%) develop duodenal cancer. Periampullary adenomas seem to carry a high risk of malignant transformation. The sensitivity of endoscopic procedures for early detection of severely dysplastic or malignant duodenal lesions is low, and the prognosis of duodenal cancer is poor. Thus the question arises whether it is possible to define a subgroup of high-risk patients for duodenal malignancy, and whether severe duodenal adenomatosis should lead to an aggressive prophylactic surgical approach. This contribution discusses the current literature and presents the experience of the Heidelberg Polyposis Register based on gastroduodenoscopy findings in 231 FAP patients. In 135 cases (58.4%) macroscopic duodenal adenomas were observed. The majority of patients displayed numerous lesions throughout the duodenum, while adenomas were restricted to the periampullary region in ten. Four patients suffered from duodenal cancer. Twenty-two required an endoscopic or operative intervention. Five were treated by laparotomy and duodenotomy, while ampullary excision was indicated in six cases. Eight patients underwent partial pancreaticoduodenectomy for severe duodenal adenomatosis.


Subject(s)
Adenoma/epidemiology , Adenomatous Polyposis Coli/epidemiology , Duodenal Neoplasms/epidemiology , Adenoma/diagnosis , Adenomatous Polyposis Coli/diagnosis , Colonoscopy , Comorbidity , Duodenal Neoplasms/diagnosis , Duodenoscopy , Female , Germany/epidemiology , Humans , Male , Prevalence , Prognosis , Registries , Risk Factors , Survival Rate
20.
Gut ; 48(4): 515-21, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11247896

ABSTRACT

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.


Subject(s)
Adenomatous Polyposis Coli/genetics , Genes, APC/genetics , Germ-Line Mutation/genetics , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli/surgery , Adult , Age of Onset , Aged , DNA Mutational Analysis , Disease Progression , Female , Genotype , Humans , Male , Middle Aged , Patient Selection , Pedigree , Phenotype , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Severity of Illness Index
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