Identification of barriers and facilitators in nationwide implementation of standardized structured reporting in pathology: a mixed method study.

Standardized structured reporting (SSR) enables high-quality pathology reporting, but implementing SSR is slow. The objective of this study is to identify both barriers and facilitators that pathologists encounter in SSR, in order to develop tailored implementation tools to increase SSR usage. We used a mixed method design: a focus group interview helped to identify barriers and facilitators in SSR. The findings were classified into the following domains: innovation, individual professional, social setting, organization, and economic and political context. We used a web-based survey among Dutch pathologists to quantify the findings. Ten pathologists participated in the focus group interview, and 97 pathologists completed the survey. The results of both showed that pathologists perceive barriers related to SSR itself. Particularly its incompatibility caused lack of nuance (73%, n = 97) in the standardized structured pathology report. Regarding the individual professional, knowledge about available SSR-templates was lacking (28%, n = 97), and only 44% (n = 94) of the respondents agreed that using SSR facilitates the most accurate diagnosis. Related to social setting, support from the multidisciplinary team members was lacking (45%, n = 94). At organization level, SSR leads to extra work (52%, n = 94) because of its incompatibility with other information systems (38%, n = 93). Main facilitators of SSR were incorporation of speech recognition (54%, n = 94) and improvement in communication during multidisciplinary team meetings (69%, n = 94). Both barriers and facilitators existed in various domains. These factors can be used to develop implementation tools to encourage SSR usage.

The incidence, mutational status, risk classification and referral pattern of gastro-intestinal stromal tumours in the Netherlands: a nationwide pathology registry (PALGA) study.

Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. From PALGA, the nationwide Dutch Pathology Registry, pathology excerpts from all patients with a GIST or GIST-like tumour between 2003 and 2012 were retrieved to calculate incidence rates. Full pathology reports were retrieved of resections in 2011 and 2012 to study the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. The incidence of GIST increased to 17.7 per million inhabitants in 2012 with a median age of 67 years. Mutational analysis was performed in 33.9% of patients with a resection between 2011 and 2012 (KIT mutation 67.5%, PDGFRA 16.3%, wild-type 11.4%). The percentage of high risk patients in the different risk classifications varied from 19.9% to 38.0% depending on the used classification. Only 35.9% of patients had diagnosis or revision of pathology diagnosis within three months in a designated GIST referral centre. No increase in proportion of central pathology reviews was found. Proportion of patients with mutational analysis increased over the years. The registered incidence of GIST, 17.7 per million inhabitants in 2012 in the Netherlands, is still rising. Despite incorporation in the ESMO GIST guidelines since 2008 for mutational testing and since 2010 for central review of pathology, both are performed in a minority of patients.

Mohs micrographic surgery of rare cutaneous tumours.

BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated with MMS at a large university centre between January 2008 and December 2012. To detect all recurrences, patients were linked to The Nationwide Network and registry of histo- and cytopathology (PALGA). RESULTS: In total, 80 patients with 80 tumours were included. Tumour types included dermatofibrosarcoma protuberans (27), atypical fibroxanthoma (22), Merkel cell carcinoma (8), microcystic adnexal carcinoma (9), sebaceous carcinoma (6), extramammary Paget's disease (2) and other (6). Mean follow-up time was 3.7 years (standard deviation 1.4) during which two atypical fibroxanthomas recurred (2.5%). CONCLUSION: This large case series shows that MMS is an appropriate treatment for rare cutaneous tumours with a recurrence rate less than 3%. Preferably, MMS for rare cutaneous tumours is performed in experienced multidisciplinary centres to further improve the quality of treatment.

The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. METHODS: Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. RESULTS: Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. CONCLUSIONS: Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.

OBJECTIVE: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes. METHODS: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated. RESULTS: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM. CONCLUSION: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.

Liver Resection for Metastatic Disease; A Population-Based Analysis of Trends.

OBJECTIVE: The study aims to evaluate all patients who underwent liver resection for metastatic disease for demographics, characteristics of the primary tumor and metastasis, volume of liver resection specimens per pathology laboratory and to describe trends in surgical treatment. METHODS: Data were prospectively collected using the Dutch nationwide pathology network. All pathology reports containing details on liver resections for metastatic disease between January 2001 and December 2010 were evaluated. RESULTS: A total of 3,916 liver resections were performed in 3,699 patients with a median age of 63 years (range 1-91). The primary tumor was mainly colorectal (n = 3,256; 88.0%). The number of 'high volume liver centers' increased from 2 to 12 in the study period, whereas the number of 'low volume centers' decreased. The number of liver resections increased from 224 to 596 per year (p ≤ 0.0001). A significant increase was demonstrated in elderly patients, patients with multiple metastases, liver resections for smaller metastases and minor liver resections. CONCLUSION: Although the majority of patients were young and had solitary metastasis, indications for liver resection are expanding as indicated by increasing numbers of elderly and patients with multiple liver metastases. Patients with non-colorectal liver metastases were seldom candidates for resection.

Chorionicity and Heritability Estimates from Twin Studies: The Prenatal Environment of Twins and Their Resemblance Across a Large Number of Traits.

There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can-like dizygotic twins-each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ's for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable.

Frequency of non-histologically diagnosed basal cell carcinomas in daily Dutch practice.

BACKGROUND: Population-based basal cell carcinoma (BCC) incidences are based on cancer registry data; however, these only include histologically diagnosed tumours. OBJECTIVES: First, to investigate the number of subsequent non-histologically diagnosed BCC(s) in patients with a first histologically diagnosed BCC in 2004. Secondly, to observe differences in tumour characteristics between subsequent histologically and subsequent non-histologically diagnosed BCC(s). METHODS: All patients, from four hospitals located in the serving area of the Eindhoven Cancer Registry, with a first histologically diagnosed BCC in 2004 (n = 1290) were selected. A linkage was made with PALGA, the nationwide network and registry of histo- and cytopathology, to obtain pathology reports of subsequent histologically diagnosed BCC(s) up to 1 November 2010. Patient records were extracted from the participating dermatology departments and reviewed up to 1 November 2010 to identify non-histologically diagnosed BCC(s). RESULTS: Overall, 33.2% of the 1089 followed up patients developed subsequent histologically and/or non-histologically diagnosed BCCs. In total, 1974 BCCs were observed of which 1833 were histologically and 141 were non-histologically diagnosed BCCs. The distribution of tumour site and subtype differed significantly between subsequent histologically and subsequent non-histologically diagnosed BCCs. CONCLUSIONS: The total burden of BCC is underestimated by the absence of data on the occurrence of non-histologically diagnosed BCCs in daily dermatological practice. It is pivotal for Dutch healthcare policy makers to acknowledge this to make accurate BCC-related cost estimates.

Cumulative risks and rates of subsequent basal cell carcinomas in the Netherlands.

BACKGROUND: The incidence of multiple basal cell carcinomas (BCCs) is not well documented. OBJECTIVES: To calculate the cumulative risks, rates and risk factors for the development of subsequent histologically confirmed BCCs. METHODS: For this cohort study the Dutch nationwide network and registry of histopathology and cytopathology (PALGA) was used. The first 2483 patients diagnosed with a first histologically confirmed BCC in the year 2004 were followed for 5years. Multifailure survival models were used to study whether gender or age affected the risk of developing subsequent tumours. RESULTS: During our observational period, the 2483 patients developed a total of 3793 histologically confirmed BCCs. The 5-year cumulative risk of developing one or more subsequent BCCs was 29·2%. Incidence rates were 25,318 per 100,000person-years in the first 6months after first BCC diagnosis, decreasing to 6953 per 100,000person-years after 5years of follow-up. Males compared with females had a 30% [adjusted hazard ratio (HR) 1·30, 95% CI (confidence interval) 1·11-1·53] higher risk of developing multiple BCCs and those aged 65-79years had more than 80% (adjusted HR 1·81, 95% CI 1·37-2·41) higher risk of having subsequent tumours compared with patients younger than 50years. CONCLUSIONS: The high incidence rate of subsequent BCCs among patients with a first BCC is highest in the first months after diagnosis of the first BCC but persists long term, indicating that patients with BCC should undergo full-body skin examinations at first presentation and subsequent follow-up visits. Special attention should be paid to males and persons of older age at index lesion.

An overview of the current diagnosis and recent developments in neuroendocrine tumours of the gastroenteropancreatic tract: the diagnostic approach.

Neuroendocrine tumours of the gastroenteropancreatic tract (GEP-NETs) comprise a group of very heterogeneous neoplasms, which are considered 'rare diseases'. Epidemiological studies on the incidence of GEP-NETs worldwide have reported a remarkable increase in the detection of these tumours. In a recent study, based on pathology reports (PALGA) to investigate the incidence of pancreatic and duodenal neuroendocrine tumours in the Netherlands from 1991 until 2009, we also noticed a significant increase in the incidence of these tumours. In particular, the incidence of non-functioning neuroendocrine tumours had significantly increased over this period. Remarkably, a substantial discrepancy was observed between the numbers of neuroendocrine tumours diagnosed in the clinical as opposed to the pathological setting, emphasising that these tumours provide a real diagnostic challenge. To improve the diagnosis of GEP -NET s, we advocate that these complex neoplasms should receive more specialised attention. In this mini-review we provide an overview of the current diagnostic approach to GEP-NETs, and add the recent developments in establishing the diagnosis of these tumours, in order to increase knowledge and awareness of GEP-NETs among clinicians and pathologists. Early detection in order to prevent morbidity from GEP-NETs is advocated.

[Recognition of congenital endometrial carcinoma: the importance of family history and investigation of microsatellite instability in the tumour]. / Herkennen van erfelijk endometriumcarcinoom: het belang van familieanamnese en onderzoek naar microsatellietinstabiliteit in de tumor.

Endometrial cancer diagnosed at a relatively young age or in a patient with a medical history of colorectal cancer may be indicative of Lynch syndrome. Four women, aged 43, 60, 41 and 54 respectively, with a family history of endometrial or colorectal neoplasm were examined for microsatellite instability (MSI) in tumour tissue with positive results. Subsequently, a mutation was found in one of the DNA mismatch repair genes. Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is caused by a germline mutation in a mismatch repair gene and is an autosomal dominant disorder that is characterized by the development of carcinoma of the endometrium and colorectum at a relatively young age. Until recently, recognition of Lynch syndrome was mainly based on an, often incomplete, family history, but today the presence of MSI in tumour tissue can be used to identify patients at risk for Lynch syndrome. A pathologist can contribute to identifying a patient at risk for Lynch syndrome by initiating MSI testing when: (a) endometrial cancer is diagnosed under the age of 50, (b) a combination of endometrial cancer and colorectal cancer is diagnosed under the age of 70.

Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer.

The cancer risk is unknown for those families in which a microsatellite instable tumour is neither explained by MLH1 promoter methylation nor by a germline mutation in a mismatch repair (MMR) gene. Such information is essential for genetic counselling. Families suspected of Lynch syndrome (n = 614) were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with those of 18 families with an unexplained microsatellite instable tumour. The mean age at diagnosis of the index patients in both groups was comparable at 44 years. Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests germline inactivation of a known gene. The Amsterdam II criteria were fulfilled in 50/75 families (66%) that carried a germline mutation in an MMR gene and in only 2/18 families (11%) with an unexplained microsatellite instable tumour (P<0.0001). Current diagnostic strategies can detect almost all highly penetrant MMR gene mutations. Patients with an as yet unexplained microsatellite instable tumour likely carry a different type of mutation that confers a lower risk of cancer for relatives.

New reference values for echocardiographic dimensions of healthy Dutch children.

AIM: To renew the echocardiographic reference values of heart dimensions in healthy children. METHODS AND RESULTS: Group 1 consisted of 587 children, of which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500 g, who visited the Pediatric Cardiology outclinic during the period January 2000 till March 2004. All included children were diagnosed as normal, or as having innocent heart murmur. The second group was taken from an earlier study and comprised 160 children (77 boys and 83 girls). The echocardiographic measures were taken from conventional M-mode recording of the left ventricle (LV) parasternal long axis view. End diastolic septal (IVS) and LV posterior wall thickness (LVPW) and end diastolic as well as end systolic LV intracavity dimensions were retrospectively analyzed. The regression lines from all measured sizes are significantly different from those collected in the early eighties. Especially the thickness of the IVS is smaller. The regression lines are independent of gender. CONCLUSIONS: New reference values have been found which should replace the presently used ones. There is no difference between boys and girls. Why the muscular wall thicknesses are thinner than found 20 years ago needs to be further explored.