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Biomedical subjects

F M Nagengast

Publications and source records attributed to F M Nagengast.

At least 19 recordsLinked to original sources
PubMed2006

[Preventive resection of hereditary diffuse gastric cancer].

Hereditary diffuse gastric cancers are rare, accounting for at most 1-3% of gastric cancers. It can be caused by a mutation in the tumour-suppressor gene CDH1. A healthy person carrying a CDH1 mutation has a cumulative risk of developing gastric cancer of 70-80%. In most cases, gastric cancer is detected before the age of 40 years. The effectiveness of screening for hereditary diffuse gastric cancer or early detection with twice-yearly upper GI endoscopy with blind biopsies is highly questionable. Given the poor prognosis of patients with hereditary diffuse gastric cancer, prophylactic gastrectomy can be considered an option for patients with a CDH1 mutation. It is recommended that the supervision, screening and possible preventative gastrectomy for hereditary diffuse gastric cancers are handled by a multidisciplinary team in a specialised centre.

Cadherins↗
PubMed2006

[Thalidomide for the treatment of recurrent gastrointestinal blood loss due to intestinal angiodysplasias].

Two female patients, 86 and 80 years of age, had been treated with blood transfusions for several years and several months, respectively, due to iron-deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were detected and subsequently coagulated in the course of repeated gastroscopies and colonoscopies. Due to the failure of this treatment, treatment with thalidomide was started. Thereafter, the gastrointestinal bleeding stopped and there was no longer any need for blood transfusions. Treatment with thalidomide seems an effective therapy for patients with frequently recurring gastrointestinal blood loss due to angiodysplasias who no longer tolerate conventional and invasive procedures due to their physical condition.

Aged, 80 and over↗
PubMed2006

What is the appropriate screening protocol in Lynch syndrome?

INTRODUCTION: Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20-25 years. It is yet unknown whether annual screening of patients aged 40-60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues. METHODS: All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected. RESULTS: A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage. At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent-child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent. CONCLUSION: The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.

Adenoma↗
PubMed2006

Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis.

BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.

Adenomatous Polyposis Coli↗
PubMed2006

Optimizing the detection of hereditary non-polyposis colorectal cancer: an update.

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominant inherited disease and accounts for up to 5% of all colorectal cancer (CRC) patients. Despite the optimization of selection criteria and enhancements in molecular techniques for identifying more families with HNPCC, most cases are not recognized. Poor patient recollection of family history and inadequate family history-taking are main causative factors. We propose a new strategy for detecting HNPCC, one in which the pathologist selects patients for microsatellite instability (MSI) testing. Criteria for MSI analysis are: (1) CRC before the age of 50 years, (2) second CRC before 70 years, (3) CRC and HNPCC-associated cancer before 70 years, or (4) adenoma before 40 years. Additionally, patients with a positive MSI test and patients with a positive family history are offered referral for genetic counselling. With this strategy, at least twice the number of HNPCC patients will be identified among a population of CRC patients, and in a cost-effective, efficient and feasible way. The identification of patients with HNPCC is important because intensive surveillance can prevent death from CRC.

Adenoma↗
PubMed2006

Low colonic glutathione detoxification capacity in patients at risk for colon cancer.

BACKGROUND: Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. MATERIALS AND METHODS: Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma (n = 64), colorectal cancer (n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. RESULTS: Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. CONCLUSIONS: An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk.

Adenoma↗
PubMed2005

[More hereditary intestinal cancer can be detected if patients with colorectal carcinoma that are selected by the pathologist are examined for microsatellite instability].

OBJECTIVE: To determine whether an investigation of microsatellite instability (MSI) in patients with colorectal carcinoma that have been selected by the pathologist could increase the number of detected families with hereditary non-polyposis colorectal carcinoma (HNPCC). DESIGN: Prospective inventory. METHOD: Pathologists selected patients with a newly diagnosed colorectal carcinoma for MSI analysis of their tumour tissue if they met one of the following four criteria: (a) colorectal carcinoma diagnosed below 50 years of age; (b) a second colorectal carcinoma; (c) a combination of colorectal carcinoma and another HNPCC-related cancer; (d) colorectal adenoma with high-grade dysplasia diagnosed below 40 years of age. Patients with a positive MSI-test were referred to a clinical geneticist. The new strategy was introduced and explored in 5 hospitals for a period of to months. RESULTS: The new strategy was adopted and implemented successfully by pathologists and surgeons and accepted with satisfaction by the patients. Of the 55 patients included, 10 had a positive MSI-test. In 8/10 patients, DNA-mutation analysis was started by the clinical geneticist and 3 germline mutations in the MSH2-gene were detected. In 2 of 3 families with a pathogenic mutation, the family history alone did not fulfil the clinical criteria for HNPCC. CONCLUSION: Selection by the pathologist for MSI investigation was feasible in daily practice and identified more HNPCC patients than selection based on family history alone.

Adult↗
PubMed2005

[Liver abscesses as a complication of Crohn's disease].

Liver abscesses were found in two women aged 23 and 34 years who suffered from Crohn's disease. The first patient was seen because of fever and thoracic pain and had been treated with infliximab. The second patient, who was pregnant, presented with abdominal pain that was thought to be due to an exacerbation of her inflammatory bowel disease. Ultrasonography and CT revealed that both patients had large liver abscesses. Both received antibiotic treatment, the first patient underwent drainage of the abscess, and the second underwent puncture twice, resulting in clinical improvements in both patients. In contrast to intra-abdominal abscesses, liver abscesses are rarely seen in patients with Crohn's disease. The clinical presentation can be mistaken for an exacerbation of Crohn's disease, but the diagnosis can be made easily using ultrasonography or CT. Treatment consists of (ultrasound-guided) percutaneous drainage and administration of antibiotics.

Adult↗
PubMed2005

A case of esophageal duplication cyst with a 13-year follow-up period.

Benign esophageal cysts are very rare embryonic malformations. In adults, esophageal cysts are mostly asymptomatic. Complications can occur due to mass effects. The diagnosis can be made using endoscopic ultrasonography (EUS), which is regarded as the diagnostic test of choice. It is a matter of debate whether relatively asymptomatic esophageal duplication cysts should be removed or whether conservative management is feasible. We report here on the case of a 37-year-old woman who presented with mild upper abdominal complaints and who was found to have compression of the distal lumen on barium esophagography. It was possible to diagnose an esophageal duplication cyst with EUS. In view of the absence of symptoms, it was decided to provide conservative management. During a 13-year follow-up period, no growth of the cyst was documented, nor did symptoms develop during this period. Close EUS observation may eliminate the need for surgery in asymptomatic patients.

Endosonography↗
PubMed2005

Cost effectiveness of a new strategy to identify HNPCC patients.

BACKGROUND: Distinguishing hereditary non-polyposis colorectal cancer (HNPCC) from non-hereditary colorectal cancer (CRC) can increase the life expectancy of HNPCC patients and their close relatives. AIM: To determine the effectiveness, efficiency, and feasibility of a new strategy for the detection of HNPCC, using simple criteria for microsatellite instability (MSI) analysis of newly detected tumours that can be applied by pathologists. Criteria for MSI analysis are: (1) CRC before age 50 years; (2) second CRC; (3) CRC and HNPCC associated cancer; or (4) adenoma before age 40 years. METHODS: The efficacy and cost effectiveness of the new strategy was evaluated against current practice. Decision analytic models were constructed to estimate the number of extra HNPCC mutation carriers and the costs of this strategy. The incremental costs and gain in life expectancy for a HNPCC mutation carrier were evaluated by Markov modelling. Feasibility was explored in five hospitals. RESULTS: Using the new strategy, 2.2 times more HNPCC patients can be identified among a CRC population compared with current practice. This new strategy was found to be cost effective with an expected cost effectiveness ratio of 3801 per life year gained. When including the group of siblings and children, the cost effectiveness ratio became 2184 per life year gained. Sensitivity analysis showed these findings to be robust. CONCLUSIONS: MSI testing in a selection of newly diagnosed CRC patients was shown to be cost effective and a feasible method to identify patients at risk for HNPCC who are not recognised by family history.

Colorectal Neoplasms↗
PubMed2004

[Recognising hereditary non-polyposis colorectal cancer without a clear family history].

In 3 patients, 2 men aged 46 and 51 years and a woman aged 54 years, with colorectal cancer there was insufficient information on the basis of the family history to diagnose 'hereditary non-polyposis colorectal cancer' (HNPCC). Further investigation showed microsatellite instability in the tumour material, an indicator for a mutation in DNA-'mismatch repair' (MMR-) genes. Immunohistochemical study of lymphocytes showed an absence of the gene products MSH2 and MSH6. Study of the MMR genes revealed a pathogenic germ-line mutation in MSH2. All three patients were satisfied with genetic testing of the MMR-genes as this gave their children and their family members the opportunity to clarify genetic status. HNPCC is a clinical diagnosis, based on family history. As family history taking is often incomplete, the diagnosis is regularly not considered. The following individual criteria can help to recognize a patient at risk for HNPCC: (a) colorectal cancer diagnosed below 50 years of age, (b) second colorectal cancer, (c) a combination of colorectal and endometrial cancer.

Base Pair Mismatch↗
PubMed2004

Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk.

Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03-2.3] and UGT1A7 (OR 2.4, 95% CI 1.3-4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.

Adult↗
PubMed2004

FDG-PET scanning in the diagnosis of gastrointestinal cancers.

This review deals with the current, well-established indications for two-(18F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning in patients with gastrointestinal cancers. FDG-PET is a non-invasive, functional imaging technique. FDG exploits the native glucose transporter to enter the cell. Since many tumours have enhanced glucose uptake, FDG is readily accumulated in malignant cells and can be detected by a PET camera. FDG-PET has been established as an important diagnostic tool in clinical oncology. This review deals with the current, well-established indications for FDG-PET scanning in patients with gastrointestinal cancers. In the current practice, FDG-PET is most commonly used to stage oesophageal carcinoma, to detect and stage recurrence of colorectal carcinoma and to differentiate between benign and malignant pancreatic lesions. The benefit of FDG-PET scanning in patients with oesophagus carcinoma is best established in stage IV disease, as the diagnostic accuracy to detect metastatic disease is higher compared to the combination of computed tomography (CT) and endoscopic ultrasound (EUS). In patients with a history of colorectal carcinoma, FDG-PET scanning is particularly effective in diagnosing recurrent disease, especially in those with a rising carcinoembryonic antigen without a suspect lesion on conventional imaging. Large series have indicated that the sensitivity and specificity for detecting recurrent colorectal carcinoma are in the range of 87%-100% and 66%-100%, respectively. Equally, FDG-PET has a high sensitivity (68%-96%) and specificity (78%-100%) in detecting pancreatic carcinoma in patients with a suspicious-looking pancreatic mass on CT scan. Lastly, we focus on the use of FDG-PET as a modality for early monitoring of treatment response in patients with gastrointestinal stromal cell tumours. Without doubt, future developments will further establish the diagnostic role of the FDG-PET scan in the care of patients with gastrointestinal cancers.

Fluorodeoxyglucose F18↗
PubMed2004

Current clinical selection strategies for identification of hereditary non-polyposis colorectal cancer families are inadequate: a meta-analysis.

Present guidelines to identify hereditary non-polyposis colorectal cancer (HNPCC) families are criticized for limitations in accuracy. The Amsterdam criteria I and II (AC I and AC II) are used to predict a germline mutation in one of the mismatch repair genes. In families not fulfilling the AC I and AC II criteria, individual indications to test cancer specimens for microsatellite instability (MSI) are guided by the Bethesda Guidelines (BG). Germline mutation testing is then performed in patients who conform to the BG and show MSI. We investigated the sensitivity and specificity of AC I, AC II, and BG. A meta-analysis of studies on the value of the AC I and AC II criteria for predicting germline mutation, as well as a meta-analysis of BG for the detection of MSI was performed. For the AC I, sensitivity varied from 54 to 91% and specificity varied from 62 to 84%. For the AC II, the pooled sensitivity was 78% and specificity ranged between 46 and 68%. Post-test probabilities of a positive test result were 0.61 and 0.46 for the AC I and AC II, respectively. Post-test probabilities of a negative test result were 0.17 and 0.21 for the AC I and AC II, respectively. For the BG, the pooled sensitivity was 89% and pooled specificity was 53%. Post-test probability of a positive test result was 41%, and post-test probability of a negative test result was 9%. The sensitivity and specificity of the Amsterdam criteria for predicting a germline mutation that causes HNPCC is not sufficient. The BG are useful for the detection of MSI in a group of patients suspected of having familial colorectal cancer (CRC), but sensitivity is very low in the total group of newly diagnosed CRC patients. Therefore, a new strategy is needed for the identification of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed2004

Hepatosplenic schistosomiasis: a review.

BACKGROUND: Schistosomiasis is a granulomatous disease that is caused by infection with schistosomes. It is a major health threat in tropical and subtropical countries. Due to increased movement, all residents of the universe are at risk of contracting this infection. The infection goes through several stages, but the most life-threatening form and leading cause of mortality is hepatosplenic schistosomiasis (HSS). It is a chronic complication, which develops as a consequence of inflammatory response. This complication has not been adequately addressed or attended the and as a consequence most of patients presenting with this complication in our settings die. OBJECTIVES: To review literature on hepatosplenic schistosomiasis, to give the state-of-the-art management of HSS, to give our own experience on management of this complication and hence impart knowledge to medical personnel on HSS. DATA SOURCE: Literature is from Medline database and experience from gastroenterology clinics. Our own experience has been blended on top. STUDY SELECTION AND DATA EXTRACTION: We have selected material, which have been verified and can be applicable in resource poor-countries, where this problem is a major health threat. DATA SYNTHESIS: Based on published studies and meta-analyses and our own experience we have been able to draw conclusions on the current understanding of the subject. CONCLUSION: Hepatosplenic schistosomiasis is a deadly complication and occurs mainly in poor countries. Regular reviews and updates of our knowledge is important to enable stakeholders of health sector understand the problem and develop strategies on its management.

Age Factors↗