Mindfulness-Based Stress Reduction in Pre-symptomatic Genetic Frontotemporal Dementia: A Pilot Study.

Pre-symptomatic frontotemporal dementia (FTD) mutation carriers and first-degree family members that are 50% at-risk for FTD may experience symptoms of anxiety and depression as a result of the ambiguity of when or if symptoms of the disease will manifest. We conducted a pilot study to investigate the use of an online mindfulness-based stress reduction (MBSR) course to reduce symptoms of anxiety and depression in presymptomatic frontotemporal dementia (FTD) mutation carriers and individuals 50% at-risk. Seven known mutation carriers and six individuals 50% at-risk completed a standardized 8-week MBSR course, and filled out pre- and post and two-month follow-up questionnaires. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS). Measures of psychological distress (SCL-90-R), coping style (UCL), quality of life (SF-36) and mindfulness skills (FFMQ) were administered as secondary outcome. Group effects were analyzed with repeated measures ANOVA or Friedman's test, and the individual reliability change index (RCI) was calculated per participant for each outcome measure. Semi-quantitative data included an evaluation and process measure post-intervention. Significant decline was found on the HADS-A post-intervention and after 2 months (p = 0.01), with 54% and 62% of participants demonstrating a clinically significant RCI, respectively. On the HADS-D, significant decline was found 2 months post-intervention (p = 0.04), which was driven by 23% of participants whom had a clinically significant RCI. Additional changes were found between baseline and post-intervention on the seeking distraction and reassuring thoughts subscales of the UCL, the depression and interpersonal sensitivity subscales of the SCL, the observe subscale of the FFMQ, and on physical role limitations of the SF-36 (all p < 0.05). The process evaluation form indicated that the course was found beneficial by participants, and that they applied it in a wide range of everyday situations. This exploratory pilot study indicates the feasibility of MBSR in reducing anxiety and depression in presymptomatic FTD mutation carriers and 50% at-risk individuals. A randomized controlled trial is necessary to replicate these results.

[Fragile X syndrome: new therapeutic strategies]. / Fragiele-X-syndroom: nieuwe therapeutische strategieën.

BACKGROUND: Fragile X syndrome (fxs) is the most common hereditary cause of intellectual disability and autism spectrum disorders. Targeted treatment is currently lacking. In the past decades an enormous amount of knowledge has been obtained concerning the involved molecular pathways, introducing potential targets for disease modifying therapy.
AIM: To present an overview of the development of targeted treatment for fxs.
METHOD: Several important publications were collected and indexed.
RESULTS: While preclinical animal model studies with targeted interventions are promising, the translation to the clinic has been disappointing.
CONCLUSION: Targeted treatment for fxs is necessary and could be applied in other causes of autism spectrum disorders and intellectual disability. Factors relating to translation, study design and outcome measures are possibly contributing to the disappointing results. The clustering of patient care in a center of expertise is required to clinically implement future therapeutic strategies and to facilitate research. In addition, this improves patient care, one example being the recent medical guideline for children with fxs.

Two novel cases expanding the phenotype of SETD2-related overgrowth syndrome.

The SETD2-related overgrowth syndrome is also called "Luscan-Lumish syndrome" (OMIM 616831) with the clinical characteristics of intellectual disability, speech delay, macrocephaly, facial dysmorphism, and autism spectrum disorders. We report on two novel patients a 4.5-year-old boy and a 23-year-old female adolescent with a speech and language developmental delay, autism spectrum disorder and macrocephaly, who were both diagnosed with SETD2-related overgrowth syndrome due to de novo frameshift mutations in the SETD2 gene. Features not previously described which were present in either one of our patients were nasal polyps, a large tongue with creases, a high pain threshold, constipation, and undescended testicles. These features may be related to the syndrome and may need special attention in future patients. Additionally, prevention of obesity should be an important point of attention for patients diagnosed with a SETD2-related overgrowth syndrome.

Intraoperative guidance in parathyroid surgery using near-infrared fluorescence imaging and low-dose Methylene Blue.

BACKGROUND: Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas. METHODS: Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma. RESULTS: A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging. CONCLUSION: Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome.

Aceruloplasminemia presents as Type 1 diabetes in non-obese adults: a detailed case series.

AIM: To detect features that might lead to the early diagnosis and treatment of aceruloplasminemia, as initiation of treatment before the onset of neurological symptoms is likely to prevent neurological deterioration. METHODS: The PubMed and OMIM databases were searched for published cases of aceruloplasminemia. Diagnostic criteria for aceruloplasminemia were undetectable or very low serum ceruloplasmin, hyperferritinemia and low transferrin saturation. Clinical, biochemical and radiological data on the presentation and follow-up of the cases were extracted and completed through e-mail contact with all authors. RESULTS: We present an overview of 55 aceruloplasminemia cases, including three previously unreported cases. Diabetes mellitus was the first symptom related to aceruloplasminemia in 68.5% of the patients, manifesting at a median age of 38.5 years, and often accompanied by microcytic or normocytic anaemia. The combination preceded neurological symptoms in almost 90% of the neurologically symptomatic patients and was found 12.5 years before the onset of neurological symptoms. CONCLUSIONS: There is a diagnostic window during which diabetes and anaemia are present although there is an absence of neurological symptoms. Screening for aceruloplasminemia in adult non-obese individuals presenting with antibody-negative, insulin-dependent diabetes mellitus and unexplained anaemia is recommended. The combination of ferritin and transferrin saturation provides a sensitive initial measure for aceruloplasminemia.

Prenatal testing for Huntington's disease in the Netherlands from 1998 to 2008.

This study aims to give an overview of the number of prenatal tests for Huntington's disease (HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987 to 1997. A total of 126 couples underwent prenatal diagnosis (PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions ≥36% or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses) resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (≥36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed.

Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.

Focusing on desired outcomes of care after colon cancer resections; hospital variations in 'textbook outcome'.

AIMS: We propose a summarizing measure for outcome indicators, representing the proportion of patients for whom all desired short-term outcomes of care (a 'textbook outcome') is realized. The aim of this study was to investigate hospital variation in the proportion of patients with a 'textbook outcome' after colon cancer resections in the Netherlands. METHODS: Patients who underwent a colon cancer resection in 2010 in the Netherlands were included in the Dutch Surgical Colorectal Audit. A textbook outcome was defined as hospital survival, radical resection, no reintervention, no ostomy, no adverse outcome and a hospital stay < 14 days. We calculated the number of hospitals with a significantly higher (positive outlier) or lower (negative outlier) Observed/Expected (O/E) textbook outcome than average. As quality measures may be more discriminative in a low-risk population, analyses were repeated for low-risk patients only. RESULTS: A total of 5582 patients, treated in 82 hospitals were included. Average textbook outcome was 49% (range 26-71%). Eight hospitals were identified as negative outliers. In these hospitals a 'textbook outcome' was realized in 35% vs. 52% in average hospitals (p < 0.01). In a sub-analysis for low-risk patients, only one additional negative outlier was identified. CONCLUSIONS: The textbook outcome, representing the proportion of patients with a perfect hospitalization, gives a simple comprehensive summary of hospital performance, while preventing indicator driven practice. Therewith the 'textbook outcome' is meaningful for patients, providers, insurance companies and healthcare inspectorate.

Nonelective colon cancer resections in elderly patients: results from the dutch surgical colorectal audit.

AIMS: The aim of the study was to assess which factors contribute to postoperative mortality, especially in elderly patients who undergo emergency colon cancer resections, using a nationwide population-based database. METHODS: 6,161 patients (1,172 nonelective) who underwent a colon cancer resection in 2010 in the Netherlands were included. Risk factors for postoperative mortality were investigated using a multivariate logistic regression model for different age groups, elective and nonelective patients separately. RESULTS: For both elective and nonelective patients, mortality risk increased with increasing age. For nonelective elderly patients (80+ years), each additional risk factor increased the mortality risk. For a nonelective patient of 80+ years with an American Society of Anesthesiologists score of III+ and a left hemicolectomy or extended resection, postoperative mortality rate was 41% compared with 7% in patients without additional risk factors. CONCLUSIONS: For elderly patients with two or more additional risk factors, a nonelective resection should be considered a high-risk procedure with a mortality risk of up to 41%. The results of this study could be used to adequately inform patient and family and should have consequences for composing an operative team.

Choosing between hospitals: the influence of the experiences of other patients.

OBJECTIVE: Publicly available information on hospital performance is increasing, with the aim to support consumers when choosing a hospital. Besides general hospital information and information on outcomes of care, there is increasing availability of systematically collected information on experiences of other patients. The aim of this study was to assess the influence of previous patients' experiences relative to other information when choosing a hospital for surgical treatment. METHODS: Three hundred thirty-seven patient volunteers and 280 healthy volunteers (response rate of 52.4% and 93.3%, respectively) filled out an Internet-based questionnaire that included an adaptive choice-based conjoint analysis. They were asked to select hospital characteristics they would use for future hospital choice, compare hospitals, and choose the overall best hospital. Based on the respondents' choices, the relative importance (RI) of each hospital characteristic for each respondent was estimated using hierarchical Bayes estimation. RESULTS: Information based on previous patients' experience was considered at least as important as information provided by hospitals. "Report card regarding physician's expertise" had the highest RI (16.83 [15.37-18.30]) followed by "waiting time for outpatient clinic appointment" (14.88 [13.42-16.34]) and "waiting time for surgery" (7.95 [7.12-8.78]). Patient and healthy volunteers considered the same hospital attributes to be important, except that patient volunteers assigned greater importance to "positive judgment about physician communication" (7.65 v. 5.80, P < 0.05) and lower importance to "complications" (2.56 v. 4.22, P < 0.05). CONCLUSION: Consumers consider patient experience-based information at least as important as hospital-based information. They rely most on information regarding physicians' expertise, waiting time, and physicians' communication when choosing a hospital.

Combining process indicators to evaluate quality of care for surgical patients with colorectal cancer: are scores consistent with short-term outcome?

OBJECTIVE: To determine if composite measures based on process indicators are consistent with short-term outcome indicators in surgical colorectal cancer care. DESIGN: Longitudinal analysis of consistency between composite measures based on process indicators and outcome indicators for 85 Dutch hospitals. SETTING: The Dutch Surgical Colorectal Audit database, the Netherlands. PARTICIPANTS: 4732 elective patients with colon carcinoma and 2239 with rectum carcinoma treated in 85 hospitals were included in the analyses. MAIN OUTCOME MEASURES: All available process indicators were aggregated into five different composite measures. The association of the different composite measures with risk-adjusted postoperative mortality and morbidity was analysed at the patient and hospital level. RESULTS: At the patient level, only one of the composite measures was negatively associated with morbidity for rectum carcinoma. At the hospital level, a strong negative association was found between composite measures and hospital mortality and morbidity rates for rectum carcinoma (p<0.05), and hospital morbidity rates for colon carcinoma. CONCLUSIONS: For individual patients, a high score on the composite measures based on process indicators is not associated with better short-term outcome. However, at the hospital level, a good score on the composite measures based on process indicators was consistent with more favourable risk-adjusted short-term outcome rates.

The relative importance of quality of care information when choosing a hospital for surgical treatment: a hospital choice experiment.

OBJECTIVE: To assess the impact of quality of care and other hospital information on patients' choices between hospitals. METHODS: 665 former surgical patients were invited to respond to an Internet-based questionnaire including a choice-based conjoint analysis. Each patient was presented with 12 different comparisons of 2 hospitals, with each hospital characterized by 6 attributes containing 2 levels. Hospital attributes were included if frequently reported by patients as most important for future hospital choices. These included both general hospital information (e.g., atmosphere), information on quality of care (e.g., percentage of patients with "textbook outcome"), and surgery-specific information (e.g., possibility for minimally invasive procedure). Hierarchial Bayes estimation was used to estimate the utilities for each attribute level for each patient. Based on the ranges of these utilities, the relative importance of each hospital attribute was determined for each participant as a measure of the impact on patients' choices. RESULTS: 308 (46.3%) questionnaires were available for analysis. Of the hospital attributes that patients considered, surgery-specific information on average had the highest relative importance (25.7 [23.9-27.5]), regardless of gender, age, and education. Waiting time and hospital atmosphere were considered least important. The attribute concerning the percentage of patients with "textbook outcomes" had the second greatest impact (18.3 [16.9-19.6]), which was similar for patients with different adverse outcome experience. CONCLUSIONS: Surgery-specific and quality of care information are more important than general information when patients choose between hospitals.

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations.

Early-onset Parkinson's disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.

Variation in case-mix between hospitals treating colorectal cancer patients in the Netherlands.

AIMS: The purpose of this study was to determine how expected mortality based on case-mix varies between colorectal cancer patients treated in non-teaching, teaching and university hospitals, or high, intermediate and low-volume hospitals in the Netherlands. MATERIAL AND METHODS: We used the database of the Dutch Surgical Colorectal Audit 2010. Factors predicting mortality after colon and rectum carcinoma resections were identified using logistic regression models. Using these models, expected mortality was calculated for each patient. RESULTS: 8580 patients treated in 90 hospitals were included in the analysis. For colon carcinoma, hospitals' expected mortality ranged from 1.5 to 14%. Average expected mortality was lower in patients treated in high-volume hospitals than in low-volume hospitals (5.0 vs. 4.3%, p < 0.05). For rectum carcinoma, hospitals expected mortality varied from 0.5 to 7.5%. Average expected mortality was higher in patients treated in non-teaching and teaching hospitals than in university hospitals (2.7 and 2.3 vs. 1.3%, p < 0.01). Furthermore, rectum carcinoma patients treated in high-volume hospitals had a higher expected mortality than patients treated in low-volume hospitals (2.6 vs. 2.2% p < 0.05). We found no differences in risk-adjusted mortality. CONCLUSIONS: High-risk patients are not evenly distributed between hospitals. Using the expected mortality as an integrated measure for case-mix can help to gain insight in where high-risk patients go. The large variation in expected mortality between individual hospitals, hospital types and volume groups underlines the need for risk-adjustment when comparing hospital performances.

The importance of experienced adverse outcomes on patients' future choice of a hospital for surgery.

OBJECTIVE: To assess whether patients who experience adverse outcomes during hospitalisation or after discharge differ in the information they would use for future choices of a hospital for surgery compared with patients without any adverse outcomes. DESIGN: Cross-sectional questionnaire study, including questions on (1) adverse outcome occurrence during hospitalisation and after discharge, (2) information patients would use for future hospital choice and (3) priority of information. SETTING: Three hospitals in the western part of The Netherlands. STUDY SAMPLE: All 2122 patients who underwent elective aorta reconstruction (for treatment of aneurysm), cholecystectomy, colon resection, inguinal hernia repair, oesophageal resection or thyroid surgery in the period 2005-2006, of whom 1329 (62.6%) responded. RESULTS: Patients who experienced postdischarge adverse outcomes intend to use more information items to choose a future hospital (on average 1.6 items more). They more often would use the item on information provision during hospitalisation (OR 2.35 (1.37 to 4.03)) and information on various quality-of-care measures, compared with patients without adverse outcomes. Patients who experienced in-hospital adverse outcomes would not use more information items but more often would use the item on mortality after surgery (OR 1.93 (1.27 to 2.94)) and extended hospital stay (OR 1.61 (1.10 to 2.36)). However, when asked for priority of information, previous treatment in that hospital is mentioned as the most important item by most patients (32%), regardless of adverse outcome occurrence, followed by hospital reputation and waiting time. CONCLUSIONS: Adverse outcome experience may change the information patients use (on quality of care) to choose a future hospital.

Surgical adverse outcome reporting as part of routine clinical care.

BACKGROUND: In The Netherlands, health professionals have created a doctor-driven standardised system to report and analyse adverse outcomes (AO). The aim is to improve healthcare by learning from past experiences. The key elements of this system are (1) an unequivocal definition of an adverse outcome, (2) appropriate contextual information and (3) a three-dimensional hierarchical classification system. OBJECTIVES: First, to assess whether routine doctor-driven AO reporting is feasible. Second, to investigate how doctors can learn from AO reporting and analysis to improve the quality of care. METHODS: Feasibility was assessed by how well doctors reported AO in the surgical department of a Dutch university hospital over a period of 9 years. AO incidence was analysed per patient subgroup and over time, in a time-trend analysis of three equal 3-year periods. AO were analysed case by case and statistically, to learn lessons from past events. RESULTS: In 19,907 surgical admissions, 9189 AOs were reported: one or more AO in 18.2% of admissions. On average, 55 lessons were learnt each year (in 4.3% of AO). More AO were reported in P3 than P1 (OR 1.39 (1.23-1.57)). Although minor AO increased, fatal AO decreased over time (OR 0.59 (0.45-0.77)). CONCLUSIONS: Doctor-driven AO reporting is shown to be feasible. Lessons can be learnt from case-by-case analyses of individual AO, as well as by statistical analysis of AO groups and subgroups (illustrated by time-trend analysis), thus contributing to the improvement of the quality of care. Moreover, by standardising AO reporting, data can be compared across departments or hospitals, to generate (confidential) mirror information for professionals cooperating in a peer-review setting.

Volume- or outcome-based referral to improve quality of care for esophageal cancer surgery in The Netherlands.

Recently, in The Netherlands esophageal resections for cancer are banned from hospitals with an annual volume less than 10. In this study we evaluate the validity of this specific volume cut-off, based on a review of the literature and an analysis of the available data on esophagectomies in our country. In addition, we compare the expected benefits of volume-based referral to the results of a regional centralization process based on differences in outcome (outcome-based referral).

Distinct genetic forms of frontotemporal dementia.

BACKGROUND: Frontotemporal dementia (FTD) is the second most common type of presenile dementia and can be distinguished into various clinical variants. The identification of MAPT and GRN defects and the discovery of the TDP-43 protein in FTD have led to the classification of pathologic and genetic subtypes. In addition to these genetic subtypes, there exist familial forms of FTD with unknown genetic defects. METHODS: We investigated the frequency, demographic, and clinical data of patients with FTD with a positive family history in our prospective cohort of 364 patients. Genetic analysis of genes associated with FTD was performed on all patients with a positive family history. Immunohistochemical studies were carried out with a panel of antibodies (tau, ubiquitin, TDP-43) in brains collected at autopsy. RESULTS: In the total cohort of 364 patients, 27% had a positive family history suggestive for an autosomal mode of inheritance, including MAPT (11%) and GRN (6%) mutations. We identified a new Gln300X GRN mutation in a patient with a sporadic FTD. The mean age at onset in GRN patients (61.8 +/- 9.9 years) was higher than MAPT patients (52.4 +/- 5.9 years). In the remaining 10% of patients with suggestive autosomal dominant inheritance, the genetic defect has yet to be identified. Neuropathologically, this group can be distinguished into familial FTLD+MND and familial FTLD-U with hippocampal sclerosis. CONCLUSION: Future genetic studies need to identify genetic defects in at least two distinct familial forms of frontotemporal dementia (FTD) with unknown genetic defects: frontotemporal lobe degeneration with ubiquitin-positive inclusions with hippocampal sclerosis and frontotemporal lobe degeneration with motor neuron disease.

Extremely long survival in six patients despite recurrent and metastatic adrenal carcinoma.

OBJECTIVE: Adrenal cortical carcinoma (ACC) is an aggressive tumour with a high mortality. We describe six patients living 12-28 years despite recurrent and/or metastatic ACC. PATIENTS: The first patient presented in 1979 with an ACC of 8 cm. After resection, she developed seven recurrences for which she was treated with resection and/or mitotane (o,p'-DDD) treatment. The patient is still alive 28 years after diagnosis. The second patient presented with an ACC of 9 cm. After resection, the patient developed liver metastases, which were treated with o,p'-DDD. The patient is still alive 25 years after diagnosis. The third patient presented with an ACC of 12 cm. The tumour was resected followed by o,p'-DDD treatment. She had a local recurrence that was completely resected. She is still alive 18 years after diagnosis. The fourth patient presented with an ACC of 14 cm. After resection, adjuvant o,p'-DDD was started. Subsequently, the patient developed two recurrences, which were resected. He is still alive 17 years after the initial diagnosis. The fifth patient presented with an ACC of 10 cm. After diagnosis, she developed lung metastasis, which were treated with o,p'-DDD and chemotherapy. The patient is still alive with slowly progressive disease 12 years after diagnosis. The sixth patient presented with an ACC of 7 cm. After resection, she developed four recurrences, which were resected. The patient is still alive 28 years after diagnosis. CONCLUSION: Some patients can have an extremely long survival of ACC, despite recurrent disease and metastases. The mainstay of therapy in our patients was repeated surgery and o,p'-DDD.