Large variation between hospitals in follow-up for colorectal cancer in southern Netherlands.

PURPOSE: The aims of the study were to describe the follow-up of colorectal cancer (CRC) patients in southern Netherlands and examine their overall and disease-free survival. METHODS: Patients newly diagnosed with CRC in 2003-2005 and 2008 with a survival of at least 1 year after diagnosis and recorded in the retrospective Eindhoven Cancer Registry were included (n = 579). Follow-up was defined as at least one liver imaging and at least two carcinoembryonic antigen (CEA) measurements. Logistic regression analyses were conducted to assess determinants of follow-up. Proportions of patients undergoing colonoscopy, CEA measurements and liver and chest imaging were calculated. Overall and disease-free survival were calculated. RESULTS: Patients ≥75 years (odds ratio (OR) 0.5 (95% confidence interval (CI) 0.3-0.7)) were less likely to receive follow-up, contrasting patients <50 years (OR 3.1 (95% CI 1.3-7.4)). In 2008, follow-up intensity increased (OR 2.3 (95% CI 1.2-4.3)), especially for liver imaging and CEA measurements. There were large differences in follow-up intensity and activities between hospitals, which were unaffected by comorbidity: ranges for colonoscopy 15-73 %, CEA measurement 46-91 % and imaging of the liver 22-70 % between hospitals. No effect of follow-up intensity was found on 5-year disease-free survival for patients aged <75 years (64 vs. 68 %; p = 0.6). Similarly, no effect of follow-up intensity on 5-year overall survival was found in these patients (77 vs. 82 %; p = 0.07). CONCLUSION: Large variation in follow-up was found for patients with CRC, mainly declining with age and hospital of follow-up. Over time, follow-up became more intensive, especially with respect to liver imaging and CEA measurements. However, follow-up consisting of at least one liver imaging and at least two CEA measurements did not improve overall and disease-free survival.

High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

Lymphatic mapping and sentinel node biopsy in Merkel's cell carcinoma.

AIM: The purpose of this study was to determine the predictive value of lymphatic mapping with selective lymphadenectomy in patients with Merkel's cell carcinoma. METHODS: Eight patients with biopsy proven Merkel's cell carcinoma underwent sentinel node biopsy. Lymphoscintigraphy was performed the day before surgery following intradermal injection of 74-111MBq of 99mTc-nanocolloid divided into four doses around the biopsy scar. Dynamic and static images were obtained. RESULTS: At least one sentinel node was visualized in all patients. The sentinel node was intra-operatively identified with the aid of a hand-held gamma probe in all cases and patent blue dye in six out of eight cases. During surgery, all sentinel nodes were successfully harvested. Metastatic cell deposits were subsequently identified in three patients (37.5%) and they underwent regional lymphadenectomy. No additional involved lymph nodes were identified. No recurrence has been reported in a median follow-up of 4.6 years (range: 8 months-10 years). CONCLUSIONS: In conclusion, sentinel node biopsy in patients with Merkel's cell carcinoma appears to be a reliable staging technique.

The sentinel node biopsy in patients with breast cancer; many controversies remain.

The sentinel node procedure has increasingly been used as a diagnostic tool for staging breast cancer. Although many institutes have embraced this procedure, many issues concerning the indications and the technique itself remain unsolved. In this review, several aspects regarding these controversies are discussed from the perspective of The Netherlands Cancer Institute. These include the definitions used to identify the sentinel node, the indications and contraindications for this procedure and the injection site of the tracer and blue dye. What are the clinical implications of a micro-metastasis in the sentinel node? What is the best treatment for patients with an involved axillary node? Should non-axillary sentinel nodes be pursued, and if so, what are the implications for further management of these patients? Finally, the current TNM system is discussed in perspective of the evolving sentinel node procedure. Although many questions remain to be solved, the regional recurrence rates are low when axillary clearance is omitted because of a tumor-free sentinel node.

Dietary antioxidants and Parkinson disease. The Rotterdam Study.

OBJECTIVE: To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD). SETTING: The community-based Rotterdam Study, the Netherlands. DESIGN: The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3). RESULTS: The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results. CONCLUSION: Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.

A population perspective on diagnostic criteria for Parkinson's disease.

For Parkinson's disease (PD), little is known about how the choice of diagnostic criteria affects research results. Using data on PD from three community studies (from Argentina, the Netherlands, Italy), we compared the impact on prevalence of several sets of diagnostic criteria. Each set was based on cardinal signs--resting tremor, bradykinesia, rigidity, impaired postural reflexes--and required that other parkinsonism be excluded. Some sets had additional requirements related to duration of symptoms, asymmetry of signs, or response to medication. In terms of prevalence, much lower estimates were associated with the requirements of asymmetry of signs and response to medication. The assessment of these clinical features may not be practical in community studies. Impaired postural reflexes, as a cardinal sign, seemed superfluous. For community studies of PD, we recommend the following diagnostic criteria: at least two of resting tremor, bradykinesia, or rigidity, in the absence of other apparent causes of parkinsonism.

APOE and the risk of PD with or without dementia in a population-based study.

OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized inhabitants from a suburb of Rotterdam, the Netherlands, aged 55 years or older. All participants were screened at baseline (1990 to 1993) and at follow-up (1993 to 1994) for symptoms of parkinsonism by study physicians; screen positives received a diagnostic workup by a neurologist. RESULTS: APOE genotyping was available for 107 PD patients (26 with and 81 without dementia) and 4,805 non-PD control subjects. The presence of at least one epsilon2 allele significantly increased the risk of PD (OR = 1.7; 95% CI, 1.0 to 2.8). When we looked separately for demented and nondemented PD patients as compared with nonparkinsonian controls, APOE did not appear to be associated with PD without dementia, but both the epsilon2 and the epsilon4 allele increased the risk of PD with dementia (OR = 5.6; 95% CI, 2.0 to 15.2 and OR = 3.6; 95% CI, 1.3 to 9.9). The risk of dementia for epsilon4 allele carriers was not significantly different for persons with or without PD. However, the epsilon2 allele strongly increased the risk of dementia in patients with PD (interaction p < 0.007). CONCLUSIONS: In the elderly the APOE-epsilon2 allele increases the risk of PD and, in particular, the risk of PD with dementia.

Prevalence of Parkinson's disease in the elderly: the Rotterdam Study.

We assessed the prevalence of Parkinson's disease (PD) in a general elderly population in the Netherlands. The study formed part of the Rotterdam Study, a population-based door-to-door study, and included 6,969 persons 55 years of age or older living in a suburb of Rotterdam, the Netherlands. All participants were examined, and those who either had at least one possible cardinal sign of parkinsonism at the neurologic screening, reported that they had PD, or were taking antiparkinsonian drugs were invited for further evaluation. The prevalence of PD in this population was 1.4% (1.2% for men, 1.5% for women). Prevalence increased with age, and prevalence figures were 0.3% for those aged 55 to 64 years, 1.0% for those 65 to 74, 3.1% for those 75 to 84, and 4.3% for those 85 to 94. The corresponding age-specific figures for men were 0.4%, 1.2%, 2.7%, and 3.0%, and for women, 0.2%, 0.8%, 3.4%, and 4.8%. Among 95- to 99-year-old women the prevalence was 5.0%. Twelve percent of the subjects with PD were detected through the screening and had not been diagnosed previously.

Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The results of seven population-based studies were examined separately and pooled to obtain age- and sex-specific estimates of the prevalence of PD. An in-person screening instrument and diagnostic clinical examination were used to detect potential PD cases. The overall prevalence (per 100 population) in persons 65 years of age and older was 1.8, with an increase from 0.6 for those age 65 to 69 years to 2.6 for those 85 to 89 years. There were no sex differences in prevalence of PD.

A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg. Dutch Multicentre PBC Study Group.

BACKGROUND: Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established. AIM: To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment. METHODS: A 6-month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3-month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months. RESULTS: Sixty-one patients were enrolled. No side-effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (- 8%; P = 0.003), aspartate aminotransferase (- 11%; P = 0.01), alanine aminotransferase (- 17%; P < 0.001), gamma-glutamyl transferase (- 34%; P < 0.001), immunoglobulin M (- 11%; P = 0.002) and cholesterol (- 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group. CONCLUSIONS: Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/ day is a suboptimal dose for treating PBC.

Intravenous pinacidil in the acute treatment of hypertension.

Pinacidil (N''-cyano-N-4-pyridyls-N'-1,2,2-trimethyl-propyl guanidine, monohydrate), a recently developed direct-acting vasodilator, was given intravenously in a dosage of 0.1-0.2 mg/kg body weight to ten untreated hypertensive patients. Pinacidil caused a fall of blood pressure from 170/108 +/- 6/3 to 156/80 +/- 5/4 mm Hg (mean +/- SE). The proportional decrease of mean arterial pressure (MAP) was 13.7 +/- 1.6%. Together with the decrease of blood pressure an increase of heart rate by 29.7 +/- 6.2% occurred. The heart rate increased by 13.6 beats/min per 10 mm Hg decrease of MAP. Pinacidil also caused significant rise of plasma noradrenaline and plasma renin activity, whereas plasma adrenaline and aldosterone remained unchanged. The serum concentrations of pinacidil and its major metabolite pinacidil-N-oxide were within the expected limits. The authors conclude that intravenously administered pinacidil causes a rapid decrease of blood pressure, but at the cost of a considerable increase of heart rate, and thus does not offer advantages over other vasodilators.

[The course of illness in ulcerative colitis]. / Het ziektebeloop bij colitis ulcerosa.

The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non-selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis-related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy.

Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds.

Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured in eight healthy volunteers after a single oral dose of the azo compounds sulphasalazine and olsalazine, the slow release compounds Pentasa, Asacol and Salofalk, and plain 5-ASA. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time, there was a significant, but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5-ASA, moreover, was excreted in faeces after the intake of azo compounds as compared with slow-release compounds.

Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: A systematic review and meta-analysis of the literature.

BACKGROUND: Sentinel node biopsy became the standard of care before consensus on the technique was reached and without randomized studies having shown a similar or decreased axillary recurrence rate. The purpose of this study was to evaluate studies reporting on patients with a negative sentinel node biopsy. METHODS: We performed a systematic review and meta-analysis of the literature for studies concerning clinically node-negative breast cancer patients with a tumour-negative sentinel node biopsy and no subsequent axillary node dissection. The axillary recurrence rate was determined, as well as the sensitivity of the sentinel node procedure and the differences in lymphatic mapping techniques. RESULTS: Forty-eight studies concerning 14 959 sentinel node-negative breast cancer patients followed for a median of 34 months were selected. Sixty-seven patients developed an axillary recurrence, resulting in a recurrence rate of 0.3%. The sensitivity of the sentinel node biopsy was 100%. Uni- and multivariable variable analyses showed that the lowest recurrence rates were reported in studies performed in cancer centres, in studies that described the use of (99m)Tc-sulphur colloid, and also when investigators used the superficial injection technique or evaluated the harvested sentinel nodes with haematoxylin-eosin and immunohistochemistry staining (p<0.01). CONCLUSIONS: In this systematic literature review, the axillary recurrence rate in sentinel node-negative patients is 0.3%, which is well within the desired range. The median sensitivity of the procedure appears to be as high as 100%. The recurrence rate is influenced by the differences in the lymphatic mapping technique.

Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds.

The disposition of 5-aminosalicylic acid (5-ASA) from 5-ASA-delivering drugs was studied in eight healthy volunteers. Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured after a single oral dose of the azo compounds sulphasalazine and olsalazine, of the slow-release compounds Pentasa, Asacol, and Salofalk, and of plain 5-ASA. Plain 5-ASA was rapidly excreted into urine and had a low faecal recovery, indicating fast absorption proximally in the intestine and little availability to the colon. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time there was a significant but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5-ASA, moreover, was excreted in faeces after intake of azo compounds as compared with slow-release compounds.

Disposition of 5-aminosalicylic acid from 5-aminosalicylic acid-delivering drugs during accelerated intestinal transit in healthy volunteers.

In eight healthy volunteers accelerated intestinal transit time was induced with bisacodyl, and urinary and faecal excretion of sulphasalazine, olsalazine, 5-aminosalicylic acid (5-ASA), and acetyl-5-ASA was studied after a single oral dose of 3.3 mmol sulphasalazine, olsalazine, Pentasa, and Salofalk and 2.6 mmol of Asacol. The faecal and urinary excretion of acetyl-5-ASA was lowest after intake of sulphasalazine and olsalazine and highest after intake of Pentasa and Salofalk. The figures for Asacol were intermediate. This indicates insufficient release of 5-ASA from sulphasalazine and olsalazine. When the results of this study are compared with those of a previous study without accelerated transit time, the disposition of 5-ASA from all the 5-ASA-delivering drugs is influenced unfavourably by an accelerated gut transit but most pronounced in the case of sulphasalazine, olsalazine, and Asacol. The impaired release from the azo compounds sulphasalazine and olsalazine is a result of far less complete splitting of the diazo bond.

Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomized multicenter study. The Ulcerative Colitis Multicenter Study Group.

Forty-nine patients with ulcerative colitis in remission were entered into a prospective, double-blind, multicenter trial comparing the relapse-preventing effect and safety of 4 g sulfasalazine and 2 g olsalazine daily during 48 wk. Of the 46 evaluable patients, 23 were assigned to sulfasalazine and 23 to olsalazine. Seven of 23 patients (30.4%) relapsed on sulfasalazine and six of 23 patients (26.1%) on olsalazine (95% confidence interval of the difference -22.0% to 30.3%). The relapse-free survival curves did not differ significantly at any time during the trial period. In both treatment groups, three patients dropped out because of adverse effects. Four patients on sulfasalazine and six patients on olsalazine experienced minor adverse effects. One patient on sulfasalazine had mild leukopenia, and four patients on sulfasalazine and one patient on olsalazine had decreased levels of haptoglobin. Thus, sulfasalazine and olsalazine are equally effective in maintaining remission of ulcerative colitis and are accompanied by a similar incidence of adverse effects.

Disposition of mesalazine from mesalazine-delivering drugs in patients with inflammatory bowel disease, with and without diarrhoea.

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol, and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from all these drugs except Pentasa.