Use of Mastectomy for Overdiagnosed Breast Cancer in the United States: Analysis of the SEER 9 Cancer Registries.

AIM: We investigated use of mastectomy as treatment for early breast cancer in the US and applied the resulting information to estimate the minimum and maximum rates at which mastectomy could plausibly be undergone by patients with overdiagnosed breast cancer. Little is currently known about overtreatments undergone by overdiagnosed patients. METHODS: In the US, screening is often recommended at ages ≥40. The study population was women age ≥40 diagnosed with breast cancer in the US SEER 9 cancer registries during 2013 (n=26,017). We evaluated first-course surgical treatments and their associations with case characteristics. Additionally, a model was developed to estimate probability of mastectomy conditional on observed case characteristics. The model was then applied to evaluate possible rates of mastectomy in overdiagnosed patients. To obtain minimum and maximum plausible rates of this overtreatment, we respectively assumed the cases that were least and most likely to be treated by mastectomy had been overdiagnosed. RESULTS: Of women diagnosed with breast cancer at age ≥40 in 2013, 33.8% received mastectomy. Mastectomy was common for most investigated breast cancer types, including for the early breast cancers among which overdiagnosis is thought to be most widespread: mastectomy was undergone in 26.4% of in situ and 28.0% of AJCC stage-I cases. These rates are substantively higher than in many European nations. The probability-based model indicated that between >0% and <18% of the study population could plausibly have undergone mastectomy for overdiagnosed cancer. This range reduced depending on the overdiagnosis rate, shrinking to >0% and <7% if 10% of breast cancers were overdiagnosed and >3% and <15% if 30% were overdiagnosed. CONCLUSIONS: Screening-associated overtreatment by mastectomy is considerably less common than overdiagnosis itself but should not be assumed to be negligible. Screening can prompt or prevent mastectomy, and the balance of this harm-benefit tradeoff is currently unclear.

Long-term relationships between screening rates, breast cancer characteristics, and overdiagnosis in US counties, 1975-2009.

Effects of mammography screening in the general population are disputed. Screening rates differ greatly between US counties, providing a natural opportunity to investigate effects of screening. We compared mammography screening rates with the types and outcomes of breast cancers diagnosed in US counties. The county screening rate was defined as the proportion of women age ≥40 with ≥1 mammogram in the past 2 years (range, 34-91%). Two periods were analyzed: 1975-2009 (612,941 breast cancer cases, 195 counties) and 1996-2009 (645,057 cases, 211-547 counties). Multiple signs of overdiagnosis were observed: First, breast cancer incidence increased as screening became common. Second, incidence stopped increasing once screening rates stabilized. Third, the increases in incidence were limited to age groups receiving screening. Fourth, the increases were larger in counties where screening became more common. Fifth, the increases were limited to small and early-stage breast cancers (which are consistent with overdiagnosis). Sixth, compensatory reductions in large and advanced-stage breast cancers were much smaller than the increases. Difference-in-differences regression analysis suggested 31% (95% CI: 28-34%) of breast cancers diagnosed in 1996-2009 were overdiagnosed. Screening rates correlated with increased incidence for all hormone receptor statuses, HER2 statuses, and grades. Reductions in breast cancer mortality during 1975-2009 were similar in screened and unscreened age groups. Overall, we found repeated signs that breast cancer overdiagnosis is widespread in the US, but the biological nature of overdiagnosed tumors remains unclear. Mortality benefits of screening, though they may be present and substantial, could not be detected at the population level.

[Advisability of biliary drainage in liver fragments reconstruction]. / Tselesoobraznost' karkasnogo drenirovaniya pri rekonstruktsii zhelcheotvedeniya fragmentarnykh transplantatov pecheni.

AIM: to estimate the effect of decompressive stented drainage of biliary anastomosis on incidence of biliary complications. MATERIAL AND METHODS: 294 patients aged from 5 months to 61 years (mean 13.8±0.81) were enrolled. They underwent liver fragments transplantation in the Department of Liver Transplantation of Petrovsky Russian Research Center of Surgery for the period from March 1997 to January 2016. Decompressive stented drainage tubes were used in 28 (9.5%) patients. Reconstruction without drainage was applied in 266 (90.5%) cases. In the group of biliobiliary reconstruction drainage was used in 18 out of 89 cases (20.2%), in the group of biliodigestive reconstruction - in 10 out of 202 cases (4.9%). Incidence of specific biliary complications was assessed. RESULTS: There was significant direct correlation of stented drainage of biliodigestive anastomosis with various biliary complications including bile leakage (r= -0,1253; p=0.06), obturation of anastomosis (r=0.045; p=0.501), stricture of anastomosis (r= -0.0665; p=0.320), other strictures of intrahepatic bile ducts (r= -0.0291; p=0.664), hepatolithiasis (r=0.0857; p=0.199). However significant direct correation was observed between stented drainage and incidence of intrahepatic bile ducts strictures (r=0.2117; p=0.046) and anastomosis obturation (r=0.2330; p=0.028) in case of biliobiliary reconstruction. Significant correation with other biliary complications was absent (p>0.05). CONCLUSION: Unconstrained stented drainage during primary biliary reconstruction is associated with increased incidence of biliary complications and should not be indicated routinely. Clear need for drainage should be determined in further investigations.

[Physical adaptation of elderly and middle aged persons in cases of spinal column osteochondrosis].

The survey covers degenerative-dystrophic processes in the spine stipulated by age as well as their influence on the quality of the elderly and middle aged persons' lives. The data of the role of physical training aimed at prophylaxis are presented. They discuss the prospective of the preventive sport technologies of athletic type as a way to solve a number of gerontological problems.

Uncertainty and variability in risk from trophic transfer of contaminants in dredged sediments.

The risks associated with bioaccumulative contaminants must be considered when evaluating dredged material disposal alternatives. The bioaccumulation of organochlorines and other contaminants by higher trophic level organisms represents one of the most significant sources of uncertainty in risk assessment. Both population variability (e.g. true population heterogeneity in body weight, lipid content, etc.) and uncertainty (e.g. measurement error) in trophic transfer can lead to large errors in predicted risk values for ecological receptors. This paper describes and quantitatively evaluates sources of uncertainty and variability in estimating the risk to an ecological receptor (osprey) from the trophic transfer of polychlorinated biphenyls (PCBs) in sediments from the New York-New Jersey (NY-NJ) Harbor. The distribution of toxicity quotients is obtained using a food chain model for the osprey and specifying distributions for input parameters, which are disaggregated to represent either uncertainty or variability. PCB concentrations in sediment and water are treated as predominantly uncertain, whereas lipid content in fish, feeding preferences, and fish weight are assumed to contribute primarily to population variability in PCB accumulation. The analysis shows that point estimates of reasonable maximum exposure (RME) exceed the uncertainty bounds on the 95th percentile of variability. The analysis also shows that uncertainties in the sediment and water contaminant concentrations contribute more to the range of risk estimates than does the variability in the population exposure parameters. The separation of uncertainty and variability in food chain models can help to support management decisions regarding dredged material disposal by providing a quantitative expression of the confidence in ecological risk estimates. A rationale is provided for the distinction between uncertain and variable parameters based on management goals and data availability.

Reconstruction of doses from radionuclide inhalation for nuclear power plant workers using air concentration measurements and associated uncertainties.

This paper presents a case study to illustrate the influence of parameter uncertainties on calculating an internal radiation dose of one actual nuclear plant worker, alias Mr. X, as well as the utility of air sampling for internal dose reconstruction. Input probability distributions for air concentrations of radionuclides were derived from empirical air measurements taken by fixed area air samplers. The total internal dose was calculated by multiplying radionuclide intake by dose conversion factors in Monte-Carlo simulations. There is significant variability in dose conversion factors and uncertainty in the estimated concentrations of radionuclides in the air to which Mr. X was exposed. The high variability and uncertainty of the model parameters contributed to large ranges of predicted internal doses for Mr. X. Two-dimensional Monte-Carlo simulations were conducted to separate contributions of the uncertainty and variability. Sensitivity analysis was conducted to determine which of the input parameters contributed most to uncertainty in internal dose estimates. Our analysis suggests that the uncertainty resulting from use of general air surveys contributes more to the internal dose ranges than the variability from DCFs and other population-derived parameters. Reduction of the uncertainty in reconstructed internal dose can be achieved by using personal air sampling and/or individual bioassays and regular whole-body counting.

Review of historical monitoring data on Techa River contamination.

The Mayak Production Association was the first Russian site for the production and separation of plutonium. The extensive increase in plutonium production during 1948-1955, as well as the absence of reliable waste-management technology, resulted in significant releases of liquid radioactive effluent into the rather small Techa River. This resulted in chronic external and internal exposure of about 30,000 residents of riverside communities; these residents form the cohort of an epidemiologic investigation. Analysis of the available historical monitoring data indicates that the following reliable data sets can be used for reconstruction of doses received during the early periods of operation of the Mayak Production Association: Temporal pattern of specific beta activity of river water for several sites in the upper Techa region since July 1951; average annual values of specific beta activity of river water and bottom sediments as a function of downstream distance for the whole river since 1951; external gamma-exposure rates near the shoreline as a function of downstream distance for the whole Techa River since 1952; and external gamma-exposure rate as a function of distance from the shoreline for several sites in the upper and middle Techa since 1951.

Strontium transfer from maternal skeleton to the fetus estimated on the basis of the Techa river data.

Measurements of 90Sr in human bone of inhabitants of the Techa river region were started in 1951, and since 1974 the Techa river population has been studied with a whole-body counter. One of the dosimetric tasks that could be decided using data on 90Sr measurements is direct evaluation of strontium transfer to the fetus from the maternal skeleton. Six cases were selected for which 90Sr measurements were available both for stillborn infants and their mothers. The ratio of 90Sr concentrations in fetal bone to maternal bone for the year of pregnancy has been evaluated. Two clusters of values were found and the difference between clusters could be explained by age-dependent features of maternal bone formation and remodelling. When the mother's 90Sr intake occurred in the period of intensive compact bone growth, the transfer coefficient was very low (0.012-0.032). If 90Sr ingestion occurred during the woman's reproductive age, the transfer to fetus was equal to 0.21-0.26.

An approach to dose reconstruction for the Urals population.

Population exposure in the Urals region occurred due to the releases of radionuclides by the Mayak plutonium facility in the 1950's. The major sources of radioactive contamination were the discharges of liquid wastes into the Techa river (1949-1956); an explosion in the storage facility for high level radioactive wastes which formed the East Urals Radioactive Trace in 1957; and gaseous aerosol releases within the first decade of the facility's operation (1949-1957). The problems of dose reconstruction for the population exposed on the Techa river banks and East Urals Radioactive Trace are outlined. The initial data sets and basic models for dose reconstruction are described. The main tasks of the Techa River Dosimetry System Project and the approaches to individual internal and external dose reassessment are formulated.

"Trion" code for radiation action calculations and its application in microdosimetry and radiobiology.

A code for calculations of electron, ion and photon radiation action on tissue-equivalent matter (water vapor) by the Monte Carlo technique is presented. The new "fluctuation detector" method is efficient in evaluating of probability distributions and moments of absorbed energy and number of ionizations in small sites. Spatial and energy distributions of particles fluences and fluctuation characteristics of radiation action on spherical and thread-like sites of nanometer diameter are compared with various experimental and theoretical data and discussed. Non-equivalence of energy absorption and ionization events and consequences of that non-equivalence are numerically analysed. As an example of radiobiological application the yield of single- and double-strand breaks of DNA is calculated in a threshold model.