Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study.

OBJECTIVES: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS: We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS: After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS: In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

[Prognosis in patients operated on for colorectal carcinoma: related to but not determined by number of lymph nodes examined]. / Prognose bij patiënten geopereerd wegens colorectaal carcinoom: wel gerelateerd aan het aantal onderzochte lymfklieren, maar niet daardoor bepaald.

The presence or absence of lymph node metastases is pivotal for the estimation of prognosis in carcinoma patients. The presence of lymph node metastases in patients with colorectal carcinoma (CRC) is an indicator of poor prognosis and adjuvant treatment is increasingly being given to these patients. For the patient much depends on effective staging of CRC. In patients with TNM stage II CRC, prognosis is related to the actual number of nodes harvested: those in whom fewer nodes are harvested fare less well. Understaging was suspected and therefore protocols now require a minimum number of nodes. Recent observational studies, however, have questioned understaging as a plausible mechanism. Tumour, biological or patient-related factors seem to be more likely. The number of nodes is not a suitable measure for the quality of pathological staging of CRC. Instead of this outcome measure, more attention should be paid to processes and future standards must be based on sound experimental evidence and not on observational surveys.

[New developments in medicine: walk-in clinics in supermarkets]. / Medische modernismen: inloopklinieken in supermarkten.

In the United States, the number of walk-in medical clinics in supermarkets is increasing rapidly. Although these clinics provide only a limited assortment of medical services, they constitute competition with primary healthcare and emergency medicine. Several factors have made the appearance of such medical clinics possible, including the strong emphasis being placed on the role of the market in medical care. It is important that the medical profession formulates the minimal standards with regard to the quality and continuity of care. Moreover, physicians must take care not to fall into the gap between the market and medical ethics. Thorough reflection regarding the essential values of the medical profession continues to be very necessary.

[On the occasion of the 65th birthday of the cervical smear: added value of population studies for cervical cancer remains unclear]. / Bij de 65e verjaardag van het uitstrijkje: onduidelijke meerwaarde van het bevolkingsonderzoek op baarmoederhalskanker.

It was in 1941 that George Papanicolaou first published his article on the use of the vaginal smear for the detection of cancer. It was generally believed that this simple test would be a blessing for women and could ultimately eradicate death from cervical cancer. Several decades later it has become clear that complexity dominates the picture of this test and not simplicity. The visual interpretation of slides, the organisation of population screening, the interpretation of its effects, quality control, viral carcinogenesis and more recently what effect the introduction of vaccination (alone and in combination) will have are the issues involved. These issues are complex to such an extent that it is almost impossible to obtain empirical evidence on the efficacy of the population-screening programme.

[Performance indicators unsuitable to monitor and improve complex health care]. / Prestatie-indicatoren ongeschikt om complexe zorg te beoordelen én te verbeteren.

Medically, socially and legally doctors are expected to deliver care of sufficient quality. Adequate quality is never self-evident. Patients and payers increasingly demand public disclosure of the condition ofhealthcare. Performance indicators have been created for this purpose, but how adequate are these measures? The problem is complex, making single performance indicators, such as the percentage of patients with traumatic hip fracture who undergo surgery within 24 hours after admission, inadequate. Improving quality requires not only proper measurement to disclose weaknesses and monitor the road to recovery but also better motivation of healthcare professionals. Pay-for-performance does not address the basic problems ofhow to measure and improve care. Doctors have to change the culture of medicine and find ways to deal with the increasing complexity of medical care.

[Cancer registries and the quality of oncological care]. / Kankerregistraties en kwaliteit van oncologische zorg.

In 1971, President Nixon of the US declared war on cancer. To ascertain what progress has been made since then, national cancer registries may provide informative data. However, if standardised morbidity and mortality summary rates for cancer are dropping, we cannot conclude that there is a causal relation between increased diagnostic or therapeutic efforts and this decline. Cancer is a biologically complex disease with more than 400 different histological types of tumour. Many different efforts are made simultaneously to improve diagnostic accuracy and therapeutic effectiveness in selected types of malignancies. Since most cancers occur in elderly people, comorbidity is also a frequent problem. Final figures are therefore influenced by many different factors. Cancer registries reflect the result of all these factors, but figures indicating progress in the war on cancer have to be interpreted with caution.

[Top 100 hospitals: varying lists, varying reputations]. / Ziekenhuizentop-100: wisselende ranglijsten, wisselende reputaties.

In the month of September no fewer than 3 different hospital rankings appeared in the media. These rankings do not reliably portray the quality of hospitals. Since they mutually differ substantially, they provide insufficient information to motivate hospitals with lower scores to make meaningful improvements, and they only partly influence the choice of patients. Another unfavourable effect of these rankings is that hospitals may begin to focus on measured factors at the expense of unmeasured factors, such as innovation, long-term goals and cooperation. Improvements in patient care can be expected to come only from the ethics of medical professionals.

[Emergency procedures for taking care of the victims of bomb attacks: logistical and medical aspects]. / De opvang van slachtoffers van bomaanslagen: logistieke en medisch-inhoudelijke aspecten.

In The Netherlands the threat of terrorist attacks also exist. Both doctors and hospitals alike should be prepared for such attacks both on the logistical as well as the medical level. Most terrorist attacks are carried out with explosives. This results in many victims and in cases of explosions in closed or semi-closed areas, often results in complex medical problems in many of the victims. An explosion that occurs as the result ofa bomb detonating can result in 4 patterns of injury: the primary explosion injury caused by the pressure of the blast, the secondary injuries caused by flying debris, the tertiary injuries caused by the explosion wind, and the quaternary caused by heat and fire. Common injuries seen following an explosion include: lung damage, neurological damage, abdominal injuries, bone fractures and skeletal damage and crush-syndrome. The triage occurs at the site of the explosion as well as on arrival in hospital. One especially important aspect of this is the sorting and selecting between victims who are likely to develop complex problems and who therefore need to receive aggressive treatment in a specially equipped centre and those patients for whom the nearest emergency department will suffice their needs. The triage should be repeated considering the possibility that initial estimates on these points may have been wrong. Epidemiological research should be carried out for each attack in order to make an inventory of the number of victims, the injuries incurred, the assessment of the effects of the medical help received and an assessment of the effectiveness of the total aid received.

[The Medical Code of Practice: clear reasons for existing, benefit less certain]. / Medisch tuchtrecht: duidelijke bestaansredenen, onzeker nut.

The Medical Code of Practice (Dutch acronym TG) aims to maintain and advance the quality of professional practice. Working together, lawyers and medical practitioners consider and make judgements on the procedures and methods practiced by caregivers. They also aim to protect citizens against the inexpert and careless execution of medical practice. Are they successful in this? Where the quality of practice is concerned, more thought must be given to the lasting effects on medical practitioners of the decisions made by the TG. Where protection ofcitizens is concerned, patients have a legal right to complain and there are various ways of doing this. Moreover, the TG is not primarily meant as a right of complaint. More empirical research is necessary into the effects of the TG.

[Performance indicators as a measure of the quality of medical care: rhetoric and reality]. / Prestatie-indicatoren als maat voor de kwaliteit van medische zorg: retoriek en realiteit.

Performance indicators may provide an indication of insufficient quality of medical care but they do not identify the cause of the problem. The political context for performance indicators is based on market ideology, where quality improvement is the goal and consumer pressure is the means. It is usually difficult to compare performance indicators among hospitals given the differences in definitions, methods of assessment, case mix, preclinical factors and data quality. Performance indicators are risk assessments and therefore subject to chance variation. Conclusions regarding performance indicators cannot be drawn due to the lack of clear, predefined benchmarks. At this time, the presence and degree of consumer pressure is unclear, and the ultimate effects of making performance factors publicly available on the quality of care is unknown. The question is whether mandatory reporting of a set of performance indicators by hospitals can provide sufficient insight into the quality of care; the measure appears to be too rough and too many factors influence the outcome. Procedure assessment is a good alternative to the use of performance indicators.

[The epidemiology of medical errors: a few issues in methodology]. / De epidemiologie van medische fouten: enkele methodologische kwesties.

Epidemiological research is needed to determine how many medical errors are made in hospitals. An estimation of error risk requires knowledge of the number of errors made and the total number of patients treated. But how do we define the term 'error'? The outcome of a medical intervention alone is insufficient; the entire treatment process has to be taken into account. For the estimation of error, two different approaches are available: retrospective chart review or prospective ethnographic observation. Both methods should account for processes and outcomes. Both methods have their limitations and can produce measurement errors. In particular, the low reproducibility of the determination of error is worrisome. To achieve safer health care, emphasis should be placed on control of processes, rather than outcomes.

[Abnormalities in tattooed skin: sometimes sarcoidosis]. / Afwijkingen in getatoeëerde huid: soms sarcoïdose.

A 43-year-old man presented with a nodular tattoo lesion on his right upperarm. Histologically it resembled the granulomatous reaction seen in systemic sarcoidosis. Further evaluation revealed asymmetrical hilar lymphadenopathy with no interstitial lung disease. Since the patient was a heavy smoker, bronchus carcinoma could not be excluded and cervical mediastinoscopy was performed in order to obtain a lymph-node biopsy. This confirmed the diagnosis of systemic sarcoidosis. The patient was treated by local application of corticosteroids, but with little result. Skin lesions in scars or tattoos may be the first symptom of systemic sarcoidosis. Skin biopsy for histological confirmation of the diagnosis is recommended, as is further investigation to evaluate other organ systems which may be affected.

[Diagnosis of pigmented skin lesions: how to recognize a malignant melanoma]. / Diagnostiek van gepigmenteerde huidafwijkingen: hoe een maligne melanoom te onderkennen.

An accurate answer to the clinical question of whether a pigmented skin lesion has become a malignant melanoma or not is difficult because of the clinical variability of this lesion. Because of the low incidence of 2400 new melanoma cases each year in The Netherlands, a general practitioner only sees one new case every 3-4 years. The best way to distinguish between a benign lesion and a malignant melanoma is the combined use of several criteria, such as in the ABCD-formula: asymmetry, border irregularity, colour variation and a diameter > 6 mm. Dermatoscopical examination, provided that the technique is used by well-trained and experienced physicians, is a valuable adjunct to clinical examination. A pigmented lesion should always be excised if there is not enough convincing evidence to exclude its malignant nature. Histological classification of pigmented lesions may prove difficult because of morphological overlap between benign and malignant melanocytic tumours.

[Sensitivity and speed of cell and tissue pre-diagnosis among breast cancer patients undergoing primary surgical treatment in two hospitals, determined with the aid of PALGA data]. / Gevoeligheid en snelheid van de voorafgaande cel- en weefseldiagnostiek bij primair chirurgisch behandelde borstkankerpatiënten in twee ziekenhuizen, bepaald met behulp van PALGA-gegevens.

OBJECTIVE: Result and process testing of cell and tissue diagnostics, including the sentinel-gland procedure, executed on patients who underwent a primary surgical intervention for mammary carcinoma. DESIGN: Retrospective. METHOD: In a group of 191 women who underwent 192 primary surgical interventions for breast cancer in 2002, data from the Pathological-Anatomical National Computerised Archive (PALGA) were examined with regard to which form of cell or tissue diagnosis was used and in how many stages the cancer diagnosis was morphologically established with sufficient certainty. RESULTS: In three-quarters of the women the diagnosis 'cancer' was established with certainty in the first stage. When the initial diagnosis was made using fine-needle cytological puncture, 35 of the 81 women had to undergo a second diagnostic test; with histological tests using needle biopsies this was 10 out of 92. The false-negative chance of fine-needle cytological tests was 13% (95% CI: 8-22) and for tests involving large-core needle biopsies 14% (95% CI: 8-23). A delay in treatment of more than 4 months occurred in 6 women due to the cancer being missed. A sentinel-gland procedure was performed on 58% of the women. In 33 women who underwent pre-operative ultrasound with fine-needle cytological testing of the axillary glands, the sensitivity for axillary gland metastases was 74% (95% CI: 53-87). CONCLUSION: Looked at in terms of the practical guideline for diagnosis of breast cancer the cell and tissue diagnoses were adequate, but the standards prescribed in that guideline for the chances of a false-negative (5%) were exceeded.

[Evaluation of frozen sections and cytological diagnosis during surgery]. / Beoordeling van vriescoupes en celdiagnostiek tijdens de operatie.

When a surgeon feels it to be necessary to carry out morphological diagnosis during the operation, the pathologist may assist him or her with rapid cell or tissue diagnosis. This must be a conscious decision to introduce an additional step into the chain of laboratory procedures from the taking of the sample to the reporting of the result. Because this additional phase requires a longer stay in the operating room and additional effort on the part of the laboratory staff, together with an increased risk of misclassification of the disease process, this step should only be taken after careful consideration of the pros en cons. On the one hand, the need for intra-operative diagnosis has decreased because of the availability of better and more accurate pre-operative diagnostic techniques; on the other hand, there are new developments such as the introduction of sentinel-node biopsy, in which one must weigh the advantages of a rapid intra-operative diagnosis against the slower but surer results of a more comprehensive lymph-node investigation. Routine examination of the cut edges during an operation is hardly ever done any longer as a result of changed biological knowledge regarding the margins needed for radical surgery.

[The yield of breast cancer screening: the importance of observational data and the problems of bias]. / De oogst van borstkankerscreening: het belang van observationele data en de problemen van bias.

Descriptive studies are important for the analysis of the effects of medical interventions. Especially in breast cancer screening, where the balance between gains and losses is often difficult to establish, detailed, empirical, long-term follow-up data on outcomes are of vital importance. Recent Dutch data comparing the prognosis, tumour stage at diagnosis and surgical treatment before and after the introduction of a population-based breast cancer screening programme reveal a better prognosis and a more favourable tumour stage after introduction of the programme. However, these data have their limitations. The interpretation of such figures is hampered by different types of bias (lead-time, length and over-diagnosis). The final assessment is always subjective and prone to confirmation bias.

[Screening: careful considerations versus commercial medicine]. / Screening: zorgvuldige afwegingen versus commerciële medicalisering.

People no longer seem to view their state of health in a light-hearted manner. The worried well hunger for every scrap of information they can find about their physical well-being, with the result that a veritable diagnostic industry is developing. Is the early detection of a disease always better than waiting for its signs or symptoms? It is difficult to answer this question and properly weigh up the beneficial effects against the side effects. Two main reasons are given for this. First of all, studies on the early detection of disease report the results selectively: beneficial effects are overstated and side effects are underreported. A more comprehensive evaluation method is needed. Secondly, new technological and therapeutic innovations are in competition with the existing techniques under investigation, which makes a long-term evaluation almost impossible. Moreover, this approach obscures questions fundamental to screening practices. There is a widening gulf between medical screening and traditional medicine, with the result that care is being transformed into a commercial product with a huge market. These developments in diagnostics pose new scientific and ethical questions that need to be answered.