Socio-economic inequality of utilization of cancer testing in Europe: A cross-sectional study.

There are currently screening programmes for breast, cervical and colorectal cancer in many European countries. However, the uptake of cancer screening in general may vary within and between countries. The aim of this study is to assess the inequalities in testing utilization by socio-economic status and whether the amount of inequality varies across European regions. We conducted an analysis based on cross-sectional data from the second wave of the European Health Interview Survey from 2013 to 2015. We analysed the use of breast, cervical, and colorectal cancer testing by socio-economic position (household income, educational level and employment status), socio-demographic factors, self-perceived health and smoking behaviour, by using multinomial logistic models, and inequality measurement based on the Slope index of inequality (SII) and Relative index of inequality (RII). The results show that the utilization of mammography (Odds Ratio (OR) = 0.55, 95% confidence interval (95%CI):0.50-0.61), cervical smear tests (OR = 0.60, 95%CI:0.56-0.65) and colorectal testing (OR = 0.82, 95%CI:0.78-0.86) was overall less likely among individuals within a low household income compared to a high household income. Also, individuals with a non-EU country of birth, low educational level and being unemployed (or retired) were overall less likely to be tested. The income-based inequality in breast (SII = 0.191;RII = 1.260) and colorectal testing utilization (SII = 0.161;RII = 1.487) was the greatest in Southern Europe. For cervical smears, this inequality was greatest in Eastern Europe (SII = 0.122;RII = 1.195). We concluded that there is considerable inequality in the use of cancer tests in Europe, with inequalities associated with household income, educational level, employment status, and country of birth.

Cost-effectiveness of the Norwegian breast cancer screening program.

The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation-wide coverage since 2005. All women aged 50-69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost-effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost-effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost-effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ∼30% in 2020 for women aged 55-80 years. The NBCSP is a highly cost-effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16-30%, at the cost of 112,162 NOK per QALY gained.

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.

Swiss Medical Board Mammography screening predictions for Switzerland: importance of time-periods.

OBJECTIVES: In 2013, the Swiss Medical Board (SMB) concluded that for three breast cancer screens over 13 years in Switzerland, cost-effectiveness was negative, with no additional benefits in quality-adjusted life-years gained. We compared these suggested predicted effects with other estimates. METHODS: We used an extensively validated model on the natural history of breast cancer in Switzerland, comparing a 13-year time frame, a life-time perspective, and a continuous screening programme, per 10,000 Swiss women. Both approaches used the Swedish randomized controlled trials for the theoretical effect. RESULTS: Over 13 years, both approaches yield comparable life-years gained (56 versus 67), but in expectation in 10,000 women's lifetimes 444 life-years are gained, and in a continuous screening programme (instead of three screens) 839 years. The SMB estimate of 56 life-years gained is counterweighted by 57 negative quality of life adjusted years, primarily resulting from a 5% annual loss for 10% of women, being false-positive results. International literature is consistent with more than four times lower losses on false-positives. The estimate of overdiagnosed cases in the 13-year time frame was four times higher than in the long-term perspective. CONCLUSIONS: By restricting life-years gained to a 13-year time frame the SMB prediction on benefits of mammography screening is unrealistically low. Predicting long-term harms and benefits, specifically tailored to observations, regarding the clinical situation before screening commences, and possible data during a screening programme, are crucial for women, professionals, and policymakers.

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

BACKGROUND: The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. METHODS: Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. RESULTS: Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. CONCLUSION: Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis.

Treatment of local-regional prostate cancer detected by PSA screening: benefits and harms according to prognostic factors.

BACKGROUND: Men with screen-detected prostate cancer can choose to undergo immediate curative treatment or enter into an expectant management programme. We quantified how the benefits and harms of immediate treatment vary according to the prognostic factors of clinical T-stage, Gleason score, and patient age. METHODS: A microsimulation model based on European Randomized Study of Screening for Prostate Cancer data was used to predict the benefits and harms of immediate treatment versus delayed treatment of local-regional prostate cancer in men aged 55-74 years. Benefits included life-years gained and reduced probability of death from prostate cancer. Harms included lead time and probability of overdiagnosis. RESULTS: The ratio of mean lead time to mean life-years gained ranged from 1.8 to 31.2, and the additional number of treatments required per prostate cancer death prevented ranged from 0.3 to 11.6 across the different prognostic groups. Both harm-benefit ratios were lowest, most favourable, for men aged 55-59 years and diagnosed with moderate-risk prostate cancer. Ratios were high for men aged 70-74 years regardless of clinical T-stage and Gleason score. CONCLUSION: Men aged 55-59 years with moderate-risk prostate cancer are predicted to derive greatest benefit from immediate curative treatment. Immediate treatment is least favourable for men aged 70-74 years with either low-risk or high-risk prostate cancer.

To be screened or not to be screened? Modeling the consequences of PSA screening for the individual.

BACKGROUND: Screening with prostate-specific antigen (PSA) can reduce prostate cancer mortality, but may advance diagnosis and treatment in time and lead to overdetection and overtreatment. We estimated benefits and adverse effects of PSA screening for individuals who are deciding whether or not to be screened. METHODS: Using a microsimulation model, we estimated lifetime probabilities of prostate cancer diagnosis and death, overall life expectancy and expected time to diagnosis, both with and without screening. We calculated anticipated loss in quality of life due to prostate cancer diagnosis and treatment that would be acceptable to decide in favour of screening. RESULTS: Men who were screened had a gain in life expectancy of 0.08 years but their expected time to diagnosis decreased by 1.53 life-years. Of the screened men, 0.99% gained on average 8.08 life-years and for 17.43% expected time to diagnosis decreased by 8.78 life-years. These figures imply that the anticipated loss in quality of life owing to diagnosis and treatment should not exceed 4.8%, for screening to have a positive effect on quality-adjusted life expectancy. CONCLUSION: The decision to be screened should depend on personal preferences. The negative impact of screening might be reduced by screening men who are more willing to accept the side effects from treatment.

Prediction of higher mortality reduction for the UK Breast Screening Frequency Trial: a model-based approach on screening intervals.

BACKGROUND: The optimal interval between two consecutive mammograms is uncertain. The UK Frequency Trial did not show a significant difference in breast cancer mortality between screening every year (study group) and screening every 3 years (control group). In this study, the trial is simulated in order to gain insight into the results of the trial and to predict the effect of different screening intervals on breast cancer mortality. METHODS: UK incidence, life tables and information from the trial were used in the microsimulation model MISCAN-Fadia to simulate the trial and predict the number of breast cancer deaths in each group. To be able to replicate the trial, a relatively low sensitivity had to be assumed. RESULTS: The model simulated a larger difference in tumour size distribution between the two groups than observed and a relative risk (RR) of 0.83 of dying from breast cancer in the study group compared with the control group. The predicted RR is lower than that reported from the trial (RR 0.93), but within its 95% confidence interval (0.63-1.37). CONCLUSION: The present study suggests that there is benefit of shortening the screening interval, although the benefit is probably not large enough to start annual screening.

Population-based mammography screening below age 50: balancing radiation-induced vs prevented breast cancer deaths.

INTRODUCTION: Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit-risk ratio of screening before age 50. METHODS: The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model. RESULTS: The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100,000 women aged 0-100 (range 1.3-6.3 extra deaths at a glandular dose of 1-5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40-74 was predicted to induce 3.7 breast cancer deaths per 100,000 women aged 0-100 (range 2.9-14.4) at biennial screening, but would also prevent 1302 deaths. CONCLUSION: The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks.

Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer.

BACKGROUND: Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated. METHODS: The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100,000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100,000 men and for United Kingdom and United States are compared. RESULTS: Without screening 2378 men per 100,000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to 60,695,000 euro. Overdetection is related to 39% of total costs (23,669,000 euro). Screening until age 75 is relatively most expensive because of the costs of overtreatment. CONCLUSION: Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.

Fenestrations in the jaws of laparoscopic graspers.

Laparoscopic graspers used for manipulating delicate tissue generally possess jaws with fenestrations (windows). The fenestrations should enhance the grip on the tissue; however, fenestrations reduce the contact area between jaws and tissue, leading to higher local pressures and possibly tissue damage. Experiments were performed to determine the effect of a fenestration on the pinch force needed to prevent slip of tissue and on the pinch force leading to tissue damage. In addition, the size and position of the fenestration were determined. Fenestrated jaws resulted in increased tissue damage, without affecting the pinch force needed to prevent slip. These negative effects increased with increasing fenestration size and when the fenestration was located toward the tip of the jaws. Therefore, fenestrated jaws had a smaller safe working range than the jaws without fenestrations.

Bowel injury as a complication of laparoscopy.

BACKGROUND: Bowel injury is a rare but serious complication of laparoscopic surgery. This review examines the incidence, location, time of diagnosis, causative instruments, management and mortality of laparoscopy-induced bowel injury. METHODS: The review was carried out using the MeSH browser within PubMed. The keywords used were 'laparoscopy/adverse effects' and 'bowel perforation'. Additional articles were sourced from references within the studies found in the PubMed search. RESULTS: The incidence of laparoscopy-induced gastrointestinal injury was 0.13 per cent (430 of 329 935) and of bowel perforation 0.22 per cent (66 of 29 532). The small intestine was most frequently injured (55.8 per cent), followed by the large intestine (38.6 per cent). In at least 66.8 per cent of bowel injuries the diagnosis was made during the laparoscopy or within 24 h thereafter. A trocar or Veress needle caused the most bowel injuries (41.8 per cent), followed by a coagulator or laser (25.6 per cent). In 68.9 per cent of instances of bowel injury, adhesions or a previous laparotomy were noted. Management was mainly by laparotomy (78.6 per cent). The mortality rate associated with laparoscopy-induced bowel injury was 3.6 per cent. CONCLUSION: At 0.13 per cent, the incidence of laparoscopy-induced bowel injury is small and such injury is usually discovered during the operation. Nevertheless, laparoscopy-induced bowel injury is associated with a high mortality rate of 3.6 per cent.

The influence of force feedback and visual feedback in grasping tissue laparoscopically.

BACKGROUND: Due to the limited force feedback provided by laparoscopic instruments, surgeons may have difficulty in applying the appropriate force on the tissue. The aim of this study was to determine the influence of force feedback and visual feedback on the exerted pinch force. METHODS: A grasper with a force sensor in the jaws was developed. Subjects with and without laparoscopic experience grasped and pulled pig bowel with a force of 5 N. The applied pinch force was measured during tasks of 1-s and 1-min duration. Visual feedback was provided in half the measurements. Force feedback was adjusted by changing the mechanical efficiency of the forceps from 30% to 90%. RESULTS: The mean pinch force applied was 6.8 N (+/-0.5), whereas the force to prevent slippage was 3.0 N (+/-0.4). Improving the mechanical efficiency had no effect on the pinch force for the 1-s measurements. The amount of excessive pinch force when holding tissue for 1 min was lower at 30% mechanical efficiency compared with 90% (105% vs 131%, p = 0.04). The tissue slipped more often when the subject had no visual feedback (2% vs 8%, p = 0.02). CONCLUSION: Force feedback and visual feedback play a more limited role than expected in the task of grasping tissue with laparoscopic forceps.

Slip and damage properties of jaws of laparoscopic graspers.

BACKGROUND: The optimal jaws of laparoscopic graspers can be used to manipulate the tissue properly with minimal damage. The criteria jaws should satisfy are investigated. METHODS: The cecum of pigs was clamped between 13 pairs of jaws differing in size and profile. Various pinch and pull forces were applied. At 5 N pull force, the minimally required pinch force to prevent slip and the pinch force that is maximally allowable without causing damage were obtained. RESULTS: With increasing size of the jaws, the contact area with the tissue increases. With increasing contact area, the pinch force leading to tissue damage was increased from 15 to 37 N. A profile of the jaws decreased the pinch force needed to prevent slip of tissue from 22 to 3 N. CONCLUSION: An optimal jaw possesses a large contact area to prevent tissue damage and a slight profile to prevent tissue slip.

The optimal mechanical efficiency of laparoscopic forceps.

BACKGROUND: Laparoscopic forceps have a large amount of friction in the mechanism, leading to a limited mechanical efficiency, which impairs the pinch force feedback. The advantage of a small amount of friction is that it is easier to maintain a constant pinch force on the tissue. Therefore, to obtain the optimal mechanical efficiency of the forceps, the influence of mechanical efficiency on the performance of several static and dynamic operative tasks, such as grasping tissue and estimating pressure, is quantified. METHODS: A grasper with adjustable mechanical efficiency and a load cell to measure the pinch force on the tissue was developed. Using this grasper, subjects performed several tasks on pig bowel tissue and simulation tissue: grasping tissue, reproducing a requested constant or variable pinch forces, and estimating the pressure in a tube. RESULTS: With increasing mechanical efficiency, a variable pinch force could be reproduced more accurately (deviation from the requested pinch force decreased from 34.4 to 24.9%, p = 0.016). The performance on the grasping tissue, reproducing a constant pinch force, and estimating pressure tasks did not improve with increased mechanical efficiency. CONCLUSIONS: The optimal mechanical efficiency of laparoscopic forceps is dependent on the task that is performed. For tasks requiring little movement of the forceps, such as grasping and holding tissue, a low mechanical efficiency is sufficient, whereas for tasks requiring repeated movement of the forceps to feel tissue, a high mechanical efficiency is required.

Inter- and intraindividual variabilities of perforation forces of human and pig bowel tissue.

BACKGROUND: A laparoscopic bowel grasper should be suitable for safely grasping the bowel in a wide variety of patients. Therefore, the inter- and intraindividual variabilities in the strength of bowel tissue to resist perforation force should be analyzed. METHODS: The large and small bowels of pigs ( n = 14) and the human small bowel ( n = 7) were clamped between two hemispheres 1.5 mm in diameter. The pinch force was increased until the tissue was perforated. RESULTS: The perforation force for the pig large bowel was higher than for the small bowel (13.5 +/- 3.7 vs 11.0 +/- 2.5 N; p = 0.014). No difference was found between the human and pig small bowel (10.3 +/- 2.9 vs 11.0 +/- 2.5 N). The intercoefficient of variation varied between 22% and 28%, and the intracoefficient of variation varied between 14% and 18%. CONCLUSIONS: The strength of the pig bowel is approximately comparable to the strength of the human bowel, and, therefore, testing of graspers on pig bowel is justified. However, due to the large interindividual variation, large safety margins should be taken into account.

Forces and displacements in colon surgery.

BACKGROUND: This study aims to find criteria for designing safer laparoscopic graspers for manipulation of delicate tissues. Since the experiment was performed in an open-surgery setup without any movement restrictions, the results are relevant to general surgery as well as laparoscopic. METHOD: Four surgeons were asked to apply via two clamps enough force to a pig's colon to stretch the mesocolon for dissection. Directions, magnitudes, and application points of the forces were recorded. RESULTS: The surgeons applied per clamp on average 2.5 N and maximally 5 N to the colon. These forces were at an angle of about 40 degrees to 70 degrees relative to the horizontal plane and approximately 60 degrees relative to each other. CONCLUSIONS: Safe laparoscopic graspers should be able to transmit at least a 5 N pull force to the tissue without damaging it. To minimize the forces used, the angles mentioned should be taken into account when placing the trocars.

Effectiveness of grasping and duration of clamping using laparoscopic graspers.

BACKGROUND: Manipulating tissue with laparoscopic forceps is more difficult than using the hands. This study investigates the effectiveness of grasping and the duration of tissue-clamping using laparoscopic forceps. METHODS: Video recordings of 10 laparoscopic colectomies and 15 cholecystectomies were analyzed using time-action analysis. RESULTS: The results indicated that 62% of the grasping actions were successful: the tissue was clamped sufficiently to perform an action. Of all the clamping actions on the colon, 10% were repeated actions. On the gallbladder 7% were repeated actions. The bowel slipped out of the grasper in 7% of the clamping actions, whereas the gallbladder slipped in 17%. In 89%, the colon was clamped less than 1 min. The maximum clamping time for colon clamps was 7 min for the colon, and 55 min for the gallbladder. CONCLUSION: The low percentage of successful grasping actions indicates that the design of laparoscopic graspers is not optimal.