The impact of body mass index on oncological and surgical outcomes of patients undergoing nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to evaluate the impact of body mass index (BMI) on oncological (primary) and surgical (secondary) outcomes of patients who underwent nephrectomy, as obesity or high BMI is a known risk factor for renal cell carcinoma (RCC) and predictor of poorer outcomes. METHODS: Studies were identified from four electronic databases from database inception to 2 June 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. The review protocol was registered in the International Prospective Register of Systematic Reviews with the identification number: CRD42021275124. RESULTS: A total of 18 studies containing 13 865 patients were identified for the final meta-analysis. Regarding oncological outcomes, higher BMI predicted higher overall survival (BMI >25 vs BMI <25 kg/m2 : hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58-0.85), cancer-specific survival (BMI >25 vs BMI <25 kg/m2 : HR 0.60, 95% CI 0.50-0.73; BMI 25-30 vs BMI <25 kg/m2 : HR 0.46, 95% CI 0.23-0.95; BMI >30 vs BMI <25 kg/m2 : HR 0.50, 95% CI 0.36-0.69), and recurrence-free survival rates (BMI >25 vs BMI <25 kg/m2 : HR 0.72, 95% CI 0.63-0.82; BMI 25-30 vs BMI <25 kg/m2 : HR 0.59, 95% CI 0.42-0.82). Those with a lower BMI fared better in surgical outcomes, such as operation time and warm ischaemic time, although the absolute difference was minimal and unlikely to be clinically significant. There was no difference between groups for length of hospital stay, intraoperative or postoperative complications, blood transfusion requirements, and conversion to open surgery. CONCLUSION: Our study suggests that a higher BMI is associated with improved long-term oncological survival and similar perioperative outcomes as a lower BMI. More research into the underlying biological and physiological mechanisms will enable better understanding of the effect of BMI, beyond mere association, on post-nephrectomy outcomes.

Effect of chitosan and gum Arabic with natamycin on the aroma profile and bacterial community of Australian grown black Périgord truffles (Tuber melansoporum) during storage.

This study aimed to assess the effect of chitosan or gum Arabic edible coatings, with natamycin (200, 300, 400 mg/L) on the aroma profiles of Western Australian grown truffles at five storage intervals: 0, 7, 14, 21, and 28 days using solid-phase microextraction (SPME)-followed by gas chromatography-mass spectrometry (GC-MS). The population structure of the bacterial community of both untreated and chitosan-natamycin (400 mg/L) coated truffles were assessed using metagenomic sequencing analysis alongside GC-MS. The results demonstrated that all the coating treatments were able to have a positive impact in halting or delaying the changes of truffle aroma throughout the storage period, with chitosan-natamycin (400 mg/L) coating having the best preservation results compared to the other coatings. Only 9 volatile organic compounds (VOCs) were found to have significant changes in chitosan-natamycin (400 mg/L) coated truffles throughout the storage period compared to 11 VOCs in untreated controls. The result also demonstrated the gradual change of fresh truffle's bacteria communities over the storage period. Over 4 weeks of storage, the dominant bacterial classes of the truffles (α-Proteobacteria, Bacteroidia or Actinobacteria classes) were replaced by Bacteroidia, Actinobacteria, Deltaprotobacteria and γ-Proteobacteria classes. The preliminary results from this study show that edible coatings can affect the VOC and bacterial communities of the truffles which may have implications for future research into truffle preservation techniques.

Reanalysis of Diesel Engine Exhaust and Lung Cancer Mortality in the Diesel Exhaust in Miners Study Cohort Using Alternative Exposure Estimates and Radon Adjustment.

The Diesel Exhaust in Miners Study (DEMS) (United States, 1947-1997) reported positive associations between diesel engine exhaust exposure, estimated as respirable elemental carbon (REC), and lung cancer mortality. This reanalysis of the DEMS cohort used an alternative estimate of REC exposure incorporating historical data on diesel equipment, engine horsepower, ventilation rates, and declines in particulate matter emissions per horsepower. Associations with cumulative REC and average REC intensity using the alternative REC estimate and other exposure estimates were generally attenuated compared with original DEMS REC estimates. Most findings were statistically nonsignificant; control for radon exposure substantially weakened associations with the original and alternative REC estimates. No association with original or alternative REC estimates was detected among miners who worked exclusively underground. Positive associations were detected among limestone workers, whereas no association with REC or radon was found among workers in the other 7 mines. The differences in results based on alternative exposure estimates, control for radon, and stratification by worker location or mine type highlight areas of uncertainty in the DEMS data.

Bogen's Critique of Linear-No-Threshold Default Assumptions.

In an article recently published in this journal, Bogen(1) concluded that an NRC committee's recommendations that default linear, nonthreshold (LNT) assumptions be applied to dose- response assessment for noncarcinogens and nonlinear mode of action carcinogens are not justified. Bogen criticized two arguments used by the committee for LNT: when any new dose adds to a background dose that explains background levels of risk (additivity to background or AB), or when there is substantial interindividual heterogeneity in susceptibility (SIH) in the exposed human population. Bogen showed by examples that SIH can be false. Herein is outlined a general proof that confirms Bogen's claim. However, it is also noted that SIH leads to a nonthreshold population distribution even if individual distributions all have thresholds, and that small changes to SIH assumptions can result in LNT. Bogen criticizes AB because it only applies when there is additivity to background, but offers no help in deciding when or how often AB holds. Bogen does not contradict the fact that AB can lead to LNT but notes that, even if low-dose linearity results, the response at higher doses may not be useful in predicting the amount of low-dose linearity. Although this is theoretically true, it seems reasonable to assume that generally there is some quantitative relationship between the low-dose slope and the slope suggested at higher doses. Several incorrect or misleading statements by Bogen are noted.

'Munchausen syndrome': a forgotten diagnosis in the spine.

PURPOSE: To present the case of a patient with Munchausen's syndrome who underwent multiple surgeries in the spine before the diagnosis was made and, therefore, to highlight the importance of this obscure condition that can result in unnecessary surgical treatment. METHODS: A 44-year-old businesswoman presented with multiple episodes of low back pain and weakness in both lower limbs over past 11 years. Past history consisted of multiple hospitalizations, and three surgeries on her lumbar spine at different hospitals, with dramatic improvement in symptoms being reported each time after surgery. Clinical examination showed inconsistent and nonspecific neurological findings. Imaging studies like X-rays, magnetic resonance imaging, and all neurophysiological studies were within normal limits. RESULTS: Multi-disciplinary evaluation by a team of orthopedicians, neurologist and psychiatrist and rehabilitation specialists diagnosed it as 'Munchausen syndrome'. Only one report of this fictitious disease in spine was found in review of literature (Association AP, Diagnostic and statistical manual of mental disorders: DSM-IV-TR(®), 2003). CONCLUSIONS: A history of multiple surgical interventions at multiple hospitals, often followed by dramatic improvement and then relapse, should trigger a suspicion of Munchausen syndrome, particularly in the scenario of normal imaging studies. Diagnosing this rare condition in spine is key to avoid unnecessary surgery.

Influence of Alternative Exposure Estimates in the Diesel Exhaust Miners Study: Diesel Exhaust and Lung Cancer.

The landmark Diesel Exhaust in Miners Study (DEMS) studied the relationship between diesel exhaust exposure (DEE) and lung cancer mortality of workers at eight nonmetal mines who were followed from beginning of dieselization of the mines (1947-1967) through December 31, 1997. The original analyses quantified DEE exposures using exposure to respirable elemental carbon (REC) to represent DEE, and CO as a surrogate for REC. However, this use of CO data, and the CO data themselves, have numerous shortcomings. We developed new estimates of REC exposures using historical data on use of diesel equipment, diesel engine horsepower (HP), mine ventilation rates, and the documented reduction in particulate matter emissions per HP in diesel engines from 1975 through 1995. These new REC estimates were applied in a conditional logistic regression of the DEMS nested case-control data very similar to the one applied in the original DEMS analyses. None of the trend slopes calculated using the new REC estimates were statistically significant (p > 0.05). Moreover, these trend slopes were smaller by roughly factors of five without control for radon exposure and factors of 12 with control for radon exposure compared to those estimated in the original DEMS analyses. Also, the 95% confidence intervals for these trend slopes had only minimal overlap with those for the slopes in the original DEMS analyses. These results underscore the uncertainty in estimates of the potency of diesel exhaust in causing lung cancer based on analysis of the DEMS data due to uncertainty in estimates of exposures to diesel exhaust.

Reanalysis of the DEMS nested case-control study of lung cancer and diesel exhaust: suitability for quantitative risk assessment.

The International Agency for Research on Cancer (IARC) in 2012 upgraded its hazard characterization of diesel engine exhaust (DEE) to "carcinogenic to humans." The Diesel Exhaust in Miners Study (DEMS) cohort and nested case-control studies of lung cancer mortality in eight U.S. nonmetal mines were influential in IARC's determination. We conducted a reanalysis of the DEMS case-control data to evaluate its suitability for quantitative risk assessment (QRA). Our reanalysis used conditional logistic regression and adjusted for cigarette smoking in a manner similar to the original DEMS analysis. However, we included additional estimates of DEE exposure and adjustment for radon exposure. In addition to applying three DEE exposure estimates developed by DEMS, we applied six alternative estimates. Without adjusting for radon, our results were similar to those in the original DEMS analysis: all but one of the nine DEE exposure estimates showed evidence of an association between DEE exposure and lung cancer mortality, with trend slopes differing only by about a factor of two. When exposure to radon was adjusted, the evidence for a DEE effect was greatly diminished, but was still present in some analyses that utilized the three original DEMS DEE exposure estimates. A DEE effect was not observed when the six alternative DEE exposure estimates were utilized and radon was adjusted. No consistent evidence of a DEE effect was found among miners who worked only underground. This article highlights some issues that should be addressed in any use of the DEMS data in developing a QRA for DEE.

Diesel engine exhaust and lung cancer mortality: time-related factors in exposure and risk.

To develop a quantitative exposure-response relationship between concentrations and durations of inhaled diesel engine exhaust (DEE) and increases in lung cancer risks, we examined the role of temporal factors in modifying the estimated effects of exposure to DEE on lung cancer mortality and characterized risk by mine type in the Diesel Exhaust in Miners Study (DEMS) cohort, which followed 12,315 workers through December 1997. We analyzed the data using parametric functions based on concepts of multistage carcinogenesis to directly estimate the hazard functions associated with estimated exposure to a surrogate marker of DEE, respirable elemental carbon (REC). The REC-associated risk of lung cancer mortality in DEMS is driven by increased risk in only one of four mine types (limestone), with statistically significant heterogeneity by mine type and no significant exposure-response relationship after removal of the limestone mine workers. Temporal factors, such as duration of exposure, play an important role in determining the risk of lung cancer mortality following exposure to REC, and the relative risk declines after exposure to REC stops. There is evidence of effect modification of risk by attained age. The modifying impact of temporal factors and effect modification by age should be addressed in any quantitative risk assessment (QRA) of DEE. Until there is a better understanding of why the risk appears to be confined to a single mine type, data from DEMS cannot reliably be used for QRA.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

BACKGROUND: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. PATIENTS AND METHODS: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload. RESULTS: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival. CONCLUSIONS: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Reduced sulfur compounds in the atmosphere of sewer networks in Australia: geographic (and seasonal) variations.

The management of odorous emissions from sewer networks has become an important issue for sewer system operators resulting in the need to better understand the composition of reduced sulfur compounds (RSCs). Gaseous RSCs including hydrogen sulfide (H2S), methanethiol (MeSH), dimethyl sulfide (DMS), carbon disulfide (CS2), dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS) were measured in the atmosphere of selected sewer networks in two major Australian cities (Sydney and Melbourne) during 2011-2012. The RSC concentrations in the sewer air were detected in a highly variable range. H2S and MeSH were found at the highest concentrations, followed by DMS (39.2-94.0 µg/m(3)), CS2 (18.3-19.6 µg/m(3)), DMDS (7.8-49.6 µg/m(3)) and DMTS (10.4-35.3 µg/m(3)). Temporal trends in the occurrence of targeted RSCs were observed and the highest sulfur concentration occurred either in summer or spring, which are typically regarded as the warmer seasons. Statistical significant difference in the magnitude of targeted RSCs was found between samples collected in Sydney and Melbourne.

Is H2S a suitable process indicator for odour abatement performance of sewer odours?

Odour abatement units are typically designed and maintained on H(2)S concentrations, but operational failures are reported in terms of overall odour removal, suggesting a wide range of malodorous compounds emitted from sewers that may not be efficiently removed by existing odour abatement processes. Towards providing greater insight into this issue, several activated carbon filters and biofilters treating odorous emissions from sewer systems in Sydney (Australia) were monitored by collecting and analysing gas samples before and after treatment. The monitoring studies were conducted by both olfactometric measurements and gas-chromatography-based chemical analysis. Single H(2)S assessment often failed to indicate the odour abatement performance for treatment systems in the abatement units studied, particularly when the incoming H(2)S concentrations were in the sub-ppm range (i.e. below H(2)S odour threshold). Chemical analysis indicated that some non-H(2)S odorous compounds were not removed efficiently during odour treatment. Additionally, when odour eliminations were correlated with the removal of individual compounds (Pearson's correlations) it was observed that the correlation (with a coefficient of 0.79) was best when the overall removal of all the measured odorous compounds that exceeded their odour threshold values was used for the analysis. These findings may help to further advance the design and operation of odour abatement processes to address the treatment of sewer odour emissions.

A statistical reevaluation of the data used in the Lanphear et al. ( 2005 ) pooled-analysis that related low levels of blood lead to intellectual deficits in children.

A pooled-analysis by Lanphear et al. (2005) of seven cohort studies of the association between blood lead (BPb) concentrations in children and measures of their intelligence concluded that "environmental lead exposure in children who have maximal blood lead levels <7.5 µg/dL is associated with intellectual deficits." This study has played a prominent role in shaping the public understanding of the effects upon children's IQ of low BPb exposures (e.g., BPb ≤ 10 µg/dL). Here we present a reanalysis of the data used by Lanphear et al. to evaluate the robustness of their conclusions. Our analysis differed from that of Lanphear et al. primarily in how we controlled for non-lead variables (allowing a number of them to be site-specific), how we defined summary measures of BPb exposure, and in how we decided which BPb measures and transformations best modeled the data. We also reproduced the Lanphear et al. analysis. Although we found some small errors and questionable decisions by Lanphear et al. that, taken alone, could cause doubt in their conclusions, our reanalysis tended to support their conclusions. We concluded that there was statistical evidence that the exposure-response is non-linear over the full range of BPb evaluated in these studies, which implies that, for a given increase in blood lead, the associated IQ decrement is greater at lower BPb levels. However at BPb below 10 µg/dL, the exposure-response is adequately modeled as linear. We also found statistical evidence for an association with IQ among children who had maximal measured BPb levels ≤7 µg/dL, and concurrent BPb levels as low as ≤5 µg/dL.

Lumbar plexopathy following instrumented posterior lumbar interbody fusion: a complication with use of Hohmann's retractor.

INTRODUCTION: A series of 12 patients in our centre following single level instrumented posterior lumbar interbody fusion at L4-L5 developed unexplainable motor weakness in the proximal lumbar nerve roots (L2, L3) and numbness of the whole limb, a clinical picture resembling lumbar plexopathy. Even though lumbar plexopathy has been reported following gynaecological procedures and in transpsoas interbody fusion surgeries, there is no literature reporting this complication following conventional instrumented posterior lumbar interbody fusions. STUDY DESIGN: Retrospective observational study. OBJECTIVE: To find the possible mechanism of development of lumbar plexopathy in patients who underwent posterior lumbar interbody fusion surgeries in our centre. MATERIAL AND METHODS: We analyzed retrospectively the medical records, electrophysiological reports of the patients, literatures on the anatomy of lumbar plexus and other literature reporting similar complications. We also dissected lumbar plexus of three cadavers and simulated surgical technique on them to find the mechanism of development of this unusual complication. RESULTS: We found injury to lumbar plexus that probably occurred intraoperatively with Hohmann's retractor that was used for retraction of the paraspinal muscles. This theory was favoured by many clinical factors and further confirmed by cadaveric dissections. CONCLUSION: We conclude that surgical technique with improper use of Hohmann's retractor causes traction and compression injury to the lumbar plexus resulting in this complication. We propose proper technique of insertion of Hohmann's retractor and also recommend use of modified Hohmann's retractor with shorter tips for spinal procedures to prevent such complication.

Extracapsular Resection of Pituitary Adenomas: A Systematic Review.

There is considerable variation in the surgical techniques for transsphenoidal excision of pituitary tumors. Recently, an extracapsular method has been developed that involves using the tumor pseudocapsule as a dissection plane to increase the extent of resection. This review assessed the outcomes of this new approach as compared with standard transsphenoidal surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE/PubMed, the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch), and LILACS databases for relevant literature and checked reference lists of relevant articles. Randomized controlled trials and prospective and retrospective cohort studies comparing extracapsular and intracapsular resection of pituitary tumors were included in the review. Five cohort studies with 1,588 participants were included. Extracapsular resection was associated with a higher likelihood of complete excision (relative risk [RR] 1.31, 95% confidence interval [CI] 1.01-1.70, p = 0.04) and endocrinologic remission (RR 1.26, 95% CI 1.03-1.54, p = 0.02). Because there was a significant risk of bias and substantial heterogeneity, the estimates of effect may not be robust. In patients with pituitary adenomas undergoing transsphenoidal excision, extracapsular resection may be associated with higher rates of complete excision and endocrinologic remission, but the evidence is not strong. Hence, randomized controlled trials to determine the magnitude of benefit and identify an improvement in progression-free or overall survival are warranted.

Mediation of work-family support and affective commitment between family supportive supervisor Behaviour and workplace deviance.

Employees' Workplace Deviant Behavior (WDB) is an organizational threat to its sustainability. This study examines the impact of the supervisors' role in improving organizational behavior because of the gap in the body of knowledge indicating the inconsistency, paucity, and uncertainties of relationships between variables when relating to their underpinning theories. The conceptualized model consists of the impact of family supportive supervisor behavior (FSSB) on workers' workplace deviant behavior (WDB) while considering Affective Commitment and Work-Family Supportive Behavior Attribution between the key variables. In terms of methodology, this quantitative study analyzed 321 valid surveys through descriptive and inferential statistics to ascertain if FSSB negatively impacts employees' WDB. As findings and novelty of this study, FSSB is found to negatively affect employees' WDB, while affective commitment mediates between FSSB and employees' WDB. Work-family supportive behavior attribution and personal life attribution of employees moderated the negative relationship between affective commitment and WDB, while work productivity attribution of employees had no significant effect as a moderator. With three (out of four) hypotheses supported by empirical evidence, this research has broadened previous studies of workers' WDB and offers organizations theoretical and practical recommendations for managing employees' WDB. More studies could be conducted in the future to address limitations in this research, examine other related theories in a new context, location, and/or culture, or select other suitable research methods.

Oxaliplatin/capecitabine vs oxaliplatin/infusional 5-FU in advanced colorectal cancer: the MRC COIN trial.

BACKGROUND: COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC). METHODS: Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment. RESULTS: In total, 64% of 2397 patients received OxCap(± cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (± cetuximab) was associated with more mucositis and infection whereas OxCap(± cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50-80 ml min(-1) on OxCap(± cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function. CONCLUSIONS: Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50-80 ml min(-1) on both regimens require close toxicity monitoring.

The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome.

BACKGROUND & AIMS: Serotonin (5-hydroxytryptamine [5-HT]) has an important role in gastrointestinal function. LX1031 is an oral, locally acting, small molecule inhibitor of tryptophan hydroxylase (TPH). Local inhibition of TPH in the gastrointestinal tract might reduce mucosal production of serotonin (5-HT) and be used to treat patients with nonconstipating irritable bowel syndrome (IBS). METHODS: We evaluated 2 dose levels of LX1031 (250 mg or 1000 mg, given 4 times/day) in a 28-day, multicenter, randomized, double-blind, placebo-controlled study of 155 patients with nonconstipating IBS. 5-hydroxyindoleacetic acid (5-HIAA), a biomarker of pharmacodynamic activity, was measured in urine samples at baseline (24 hours after LX1031 administration), and at weeks 4 and 6 (n = 76). RESULTS: Each dose of LX1031 was safe and well-tolerated. The primary efficacy end point, relief of IBS pain and discomfort, improved significantly in patients given 1000 mg LX1031 (25.5%), compared with those given placebo, at week 1 (P = .018); with nonsignificant improvements at weeks 2, 3, and 4 (17.9%, 16.3%, and 11.6%, respectively). Symptom improvement correlated with a dose-dependent reduction in 5-HIAA, a marker for TPH inhibition, from baseline until week 4. This suggests the efficacy of LX1031 is related to the extent of inhibition of 5-HT biosynthesis. Stool consistency significantly improved, compared with the group given placebo, at weeks 1 and 4 (P < .01) and at week 2 (P < .001). CONCLUSIONS: In a phase 2 study, LX1031 was well tolerated, relieving symptoms and increasing stool consistency in patients with nonconstipating IBS. Symptom relief was associated with reduced levels of 5-HIAA in urine samples. This marker might be used to identify patients with nonconstipating IBS who respond to inhibitors of 5-HT synthesis.

A meta-analysis of evidence for hormesis in animal radiation carcinogenesis, including a discussion of potential pitfalls in statistical analyses to detect hormesis.

A database containing 800 datasets on the incidence of specific tumor types from 262 radiation carcinogenicity experiments identified in a comprehensive literature search through September 2000 was analyzed for evidence of hormesis. This database includes lifetime studies of tumorigenic responses in mice, rats, and dogs to exposures to alpha, beta, gamma, neutron, or x-ray radiation. A J-shaped dose response, in the form of a significant decreased response at some low dose followed by a significant increased response at a higher dose, was found in only four datasets from three experiments. Three of these datasets involved the same control animals and two also shared dosed animals; the J shape in the fourth dataset appeared to be the result of an outlier within an otherwise monotonic dose response. A meta-analysis was conducted to determine whether there was an excess of dose groups with decreases in tumor response below that in controls at doses below no-observed-effect levels (NOELs) in individual datasets. Because the probability of a decreased response is generally not equal to the probability of an increased response even in the null case, the meta-analysis focused on comparing the number of statistically significant diminished responses to the number expected, assuming no dose effect below the NOEL. Only 54 dose groups out of the total of 2579 in the database had doses below the dataset-specific NOEL and that satisfied an a priori criterion for sufficient power to detect a reduced response. Among these 54, a liberal criterion for defining a significant decreases identified 15 such decreases, versus 54 × 0.2 = 10.8 expected. The excess in significant reductions was accounted for almost entirely by the excess from neutron experiments (10 observed, 6.2 expected). Nine of these 10 dose groups involved only 2 distinct control groups, and 2 pairs from the 10 even shared dosed animals. Given this high degree of overlap, this small excess did not appear remarkable, although the overlap prevented a formal statistical analysis. A comprehensive post hoc evaluation using a range of NOEL definitions and alternative ways of restricting the data entering the analysis did not produce materially different results. A second meta-analysis found that, in every possible low dose range ([0, d] for every dose, d) of each of the radiation types, the number of dose groups with significantly increased tumorigenic responses was either close to or exceeded the number showing significantly reduced responses. This meta-analysis was considered to be the more definitive one. Not only did it take dose into account by looking for consistent evidence of hormesis throughout defined low-dose ranges, it was also potentially less susceptible to limitations in experimental protocols that would cause individual animals to respond in a non-independent fashion. Overall, this study found little evidence in a comprehensive animal radiation database to support the hormesis hypothesis. However, the ability of the database to detect a hormetic effect was limited both by the small number of dose groups with doses below the range where positive effects have been found in epidemiological studies (≤ 0.1 Gy) and by the limited power of many of these dose groups for detecting a decrease in response.