A noncanonical enzymatic function of PIWIL4 maintains genomic integrity and leukemic growth in AML.

RNA-binding proteins (RBPs) form a large and diverse class of factors, many members of which are overexpressed in hematologic malignancies. RBPs participate in various processes of messenger RNA (mRNA) metabolism and prevent harmful DNA:RNA hybrids or R-loops. Here, we report that PIWIL4, a germ stem cell-associated RBP belonging to the RNase H-like superfamily, is overexpressed in patients with acute myeloid leukemia (AML) and is essential for leukemic stem cell function and AML growth, but dispensable for healthy human hematopoietic stem cells. In AML cells, PIWIL4 binds to a small number of known piwi-interacting RNA. Instead, it largely interacts with mRNA annotated to protein-coding genic regions and enhancers that are enriched for genes associated with cancer and human myeloid progenitor gene signatures. PIWIL4 depletion in AML cells downregulates the human myeloid progenitor signature and leukemia stem cell (LSC)-associated genes and upregulates DNA damage signaling. We demonstrate that PIWIL4 is an R-loop resolving enzyme that prevents R-loop accumulation on a subset of AML and LSC-associated genes and maintains their expression. It also prevents DNA damage, replication stress, and activation of the ATR pathway in AML cells. PIWIL4 depletion potentiates sensitivity to pharmacological inhibition of the ATR pathway and creates a pharmacologically actionable dependency in AML cells.

Benchmarking gambling screens to health-state utility: the PGSI and the SGHS estimate similar levels of population gambling-harm.

BACKGROUND: Both the Problem Gambling Severity Index (PGSI) and the Short Gambling Harms Screen (SGHS) purport to identify individuals harmed by gambling. However, there is dispute as to how much individuals are harmed, conditional on their scores from these instruments. We used an experienced utility framework to estimate the magnitude of implied impacts on health and wellbeing. METHODS: We measured health utility using the Short Form Six-Dimension (SF-6D), and used this as a benchmark. All 2603 cases were propensity score weighted, to balance the affected group (i.e., SGHS 1+ or PGSI 1+ vs 0) with a reference group of gamblers with respect to risk factors for gambling harm. Weighted regression models estimated decrements to health utility scores attributable to gambling, whilst controlling for key comorbidities. RESULTS: We found significant attributable decrements to health utility for all non-zero SGHS scores, as well as moderate-risk and problem gamblers, but not for PGSI low-risk gamblers. Applying these coefficients to population data, we find a similar total burden for both instruments, although the SGHS more specifically identified the subpopulation of harmed individuals. For both screens, outcomes on the SF-6D implies that about two-thirds of the 'burden of harm' is attributable to gamblers outside of the most severe categories. CONCLUSIONS: Gambling screens have hitherto provided nominal category membership, it has been unclear whether moderate or 'at-risk' scores imply meaningful impact, and accordingly, population surveys have typically focused on problem gambling prevalence. These results quantify the health utility decrement for each category, allowing for tracking of the aggregate population impact based on all affected gamblers.

Stressful Life Events Precede Gambling Problems, and Continued Gambling Problems Exacerbate Stressful Life Events; A Life Course Calendar Study.

Do stressful life events cause gambling problems, or do gambling problems cause stressful life events? This study used a retrospective design to examine the temporal order of these associations. Specifically, the study employed a life course calendar in a self-directed online survey to minimise memory biases common in retrospective designs. A total of 1564 US respondents who had gambled at any point in their life (51.0% female, median age 46) were asked whether, for each year of their adult life, they had experienced each of eight stressful life events, and whether they had engaged in casual or heavy gambling, drinking or drug use, with heavy gambling defined in line with a problem gambling definition. We found that five stressful life events were associated with the onset of heavy gambling: work issues, financial issues, legal issues, relationship issues and the death of a loved one. The same five stressful life events predict the cessation of an episode of heavy gambling, indicating a possible tendency for gambling problems to self-resolve in the presence of stress. Insights are also gained into comorbidities with alcohol and drug use, and the course of stressful life events and gambling and substance use throughout the life course, albeit with a non-representative sample. The methodology allows tentative conclusions in terms of possible causation pathways, indicating that stressful life events may play a role both in the onset and the maintenance (or cessation) of gambling problems.

A framework for indirect elicitation of the public health impact of gambling problems.

Gambling problems are increasingly understood as a health-related condition, with harms from excessive time and money expenditure contributing to significant population morbidity. In many countries, the prevalence of gambling problems is known with some precision. However, the true severity of gambling problems in terms of their impact on health and wellbeing is the subject of ongoing debate. We firstly review recent research that has attempted to estimate harm from gambling, including studies that estimate disability weights using direct elicitation. Limitations of prior approaches are discussed, most notably potential inflation due to non-independent comorbidity with other substance use and mental health conditions, and potential biases in the subjective attribution of morbidity to gambling. An alternative indirect elicitation approach is outlined, and a conceptual framework for its application to gambling is provided. Significant risk factors for propensity to develop gambling problems are enumerated, and relative risks for comorbidities are calculated from recent meta-analyses and reviews. Indirect elicitation provides a promising alternative framework for assessing the causal link between gambling problems and morbidity. This approach requires implementation of propensity score matching to estimate the counterfactual, and demands high quality information of risk factors and comorbid conditions, in order to estimate the unique contribution of gambling problems. Gambling harm is best understood as a decrement to health utility. However, achieving consensus on the severity of gambling problems requires triangulation of results from multiple methodologies. Indirect elicitation with propensity score matching and accounting for comorbidities would provide an important step towards full integration of gambling within a public health paradigm.

What's the Message? A Content Analysis of Emails and Texts Received from Wagering Operators During Sports and Racing Events.

Previous research has established direct messages (such as emails and text messages) are a widely seen form of advertising and are highly influential on sports betting and race betting behaviour. Nevertheless, few studies have examined the specific content of these messages, and whether their content is related to account-holders' betting behaviour. The current study used an ecological momentary assessment design to examine direct messages received from wagering operators during the week around major Australian sports and racing events. Respondents completed a baseline survey followed by short daily surveys over a period of 1 week during peak betting periods, and provided the research team with the emails and text messages they received from wagering operators during this time. A sample of 102 sports and 110 race bettors provided a total of 931 messages. These messages subsequently underwent a content analysis to extract key features that were promoted, including inducements, incentives, and bet type. The analysis found the messages were saturated with inducements to bet, however no relationships were identified between the content of messages and the gambling risk status or betting frequency of participants. The most common types of incentives offered included bonus bets, rewards points, better odds/winnings, and reduced risk. Frequently promoted inducements included bonus or better winnings, refund/stake back offers, and match your stake/deposit. Given the influences of inducements on increasing betting expenditure and impulsive betting identified through previous research, taken together with the findings of the current study, direct messages may contribute to experiencing gambling-related harm. These findings have important implications for consumer education and the regulation of direct messages.

Til Debt Do Us Part: Comparing Gambling Harms Between Gamblers and Their Spouses.

This study compared the experience of gambling related harms between gamblers and spouses, whilst taking into account gender and problem gambling severity. Participants (N = 5036, 2603 females) from Australia and New Zealand completed a retrospective survey that probed the prevalence of specific harms from gambling within six harm domains (financial, work/study, health, emotional/psychological, relationship, and social deviance). Overall there was a similar count of total harms reported across all domains experienced by spouses (vs gamblers), however the types and patterns of harms reported were markedly different. Spouses reported the highest number of harms within the emotional/psychological and relationship domains, whereas gamblers experienced a higher number of harms in all other domains. Spouses were five to six times more likely to report increased conflict in their relationship due to gambling, greater relationship tension, and ending a relationship. In comparison, gamblers reported more severe health-related harms, such as suicide attempts and increased alcohol consumption. The findings highlight the unique ways in which gamblers and their spouses each respond to the presence of gambling problems.

A tale of two countries: comparing disability weights for gambling problems in New Zealand and Australia.

PURPOSE: This study aimed to assess the impact of gambling problems on quality of life. Specifically, we generated disability weight estimates for gambling problems in New Zealand, and compared these results with (i) Australian figures (J Gambl Issues, 10.4309/jgi.v0i36.3978, 2017) and (ii) other health states (Lancet, 10.1016/S0140-6736(12)61680-8, 2013); such as anxiety and alcohol use disorders. METHOD: The 324 participants (48 experts and 276 general population members) evaluated a series of gambling harm vignettes. The participants rated the decrement to one's quality of life using Visual Analogue Scale and Time Trade-Off protocols (Br Med Bull, 10.1093/bmb/ldq033, 2010). These evaluations enabled the calculation of disability weights for three categories of gamblers (low-risk, moderate-risk, and problem gamblers). RESULTS: Disability weight estimates for low-risk, moderate-risk, and problem gamblers in NZ were consistently higher than the Australian weights: low (0.18 vs. 0.13), moderate (0.37 vs. 0.29), and problem (0.54 vs. 0.44). The quality of life impact for problem gambling in NZ (0.54) was comparable to that experienced in severe alcohol use disorder (0.55) (Lancet, 10.1016/S0140-6736(12)61680-8, 2013). CONCLUSIONS: This study represents one of the first attempts to assess gambling-related harm through a public health perspective. The results of this study are informative for policy-making, resource allocation, and service planning. These estimates now allow for the population-level impact of gambling in NZ to be calculated and tracked over time, which is essential for informing harm-minimisation initiatives.

Breaking Bad: Comparing Gambling Harms Among Gamblers and Affected Others.

This article examines gambling harms from both gamblers and affected others' perspectives. Participants (3076 gamblers and 2129 affected others) completed a retrospective survey that elicited information on harms they experienced from gambling across their lifetime. Their responses were analyzed through testing measurement invariance, estimating item-response theoretic parameters, calculating percentages, confidence intervals, and correlations, as well as regressions. The results indicated large commonalities in the experience of harms reported by gamblers and affected others. Further, gamblers appeared to 'export' about half of the harms they experienced to those around them. The findings also provided detailed profiles of evolving harms as problem gambling severity varies.

Beyond Hox: the role of ParaHox genes in normal and malignant hematopoiesis.

During the past decade it was recognized that homeobox gene families such as the clustered Hox genes play pivotal roles both in normal and malignant hematopoiesis. More recently, similar roles have also become apparent for members of the ParaHox gene cluster, evolutionarily closely related to the Hox gene cluster. This is in particular found for the caudal-type homeobox genes (Cdx) genes, known to act as upstream regulators of Hox genes. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. Correlative studies indicate that CDX2 functions as master regulator of perturbed HOX gene expression in human acute myeloid leukemia, locating this ParaHox gene at a central position for initiating and maintaining HOX gene dysregulation as a driving leukemogenic force. There are still few data about potential upstream regulators initiating aberrant CDX2 expression in human leukemias or about critical downstream targets of CDX2 in leukemic cells. Characterizing this network will hopefully open the way to therapeutic approaches that target deregulated ParaHox genes in human leukemia.

High expression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable prognostic factor in cytogenetically normal acute myeloid leukemia.

Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor of Wnt signaling. We recently showed that aberrant LEF1 expression induces acute myeloid leukemia (AML) in mice, and found high LEF1 expression in a subset of cytogenetically normal AML (CN-AML) patients. Whether LEF1 expression associates with clinical and molecular patient characteristics and treatment outcomes remained unknown. We therefore studied LEF1 expression in 210 adults with CN-AML treated on German AML Cooperative Group trials using microarrays. High LEF1 expression (LEF1high) associated with significantly better relapse-free survival (RFS; P < .001), overall survival (OS; P < .001), and event-free survival (EFS; P < .001). In multivariable analyses adjusting for established prognosticators, LEF1high status remained associated with prolonged RFS (P = .007), OS (P = .01), and EFS (P = .003). In an independent validation cohort of 196 CN-AML patients provided by the German-Austrian AML Study Group, LEF1high patients had significantly longer OS (P = .02) and EFS (P = .04). We validated the prognostic relevance of LEF1 expression by quantitative PCR, thereby providing a clinically applicable platform to incorporate this marker into future risk-stratification systems for CN-AML. Gene-expression profiling and immunophenotyping revealed up-regulation of lymphopoiesis-related genes and lymphoid cell-surface antigens in LEF1high patients. In summary, we provide evidence that high LEF1 expression is a novel favorable prognostic marker in CN-AML.

Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia.

A challenge for the development of therapies selectively targeting leukemic stem cells in acute myeloid leukemia (AML) is their similarity to normal hematopoietic stem cells (HSCs). Here we demonstrate that the leukemia-propagating cell in murine CALM/AF10-positive AML differs from normal HSCs by B220 surface expression and immunoglobulin heavy chain rearrangement. Furthermore, depletion of B220+ cells in leukemic transplants impaired development of leukemia in recipients. As in the murine model, human CALM/AF10-positive AML was characterized by CD45RA (B220)-positive, IG DH-JH rearranged leukemic cells. These data demonstrate in a murine leukemia model that AML can be propagated by a transformed progenitor with lymphoid characteristics, which can be targeted by antibodies that do not crossreact with normal HSCs.

Harm-to-self from gambling: A national study of Australian adults.

Aims: Understanding how gambling harm is distributed is essential to inform effective harm reduction measures. This first national Australian study of gambling harm-to-self examined the extent, distribution, risk factors, and health related quality of life (HRQoL) impacts of this harm. Methods: A Random Digit Dialling sample of 15,000 Australian adults was weighted to key population variables. Key measures included the Gambling Harms Scale-10 (GHS-10), PGSI, SF-6D, gambling behaviours, and demographics. Analyses included ordinal logistic regression. Results: Amongst gamblers, 14.7% reported harm on the GHS-10, including 1.9% reporting high-level harm. While high-level harm occurred mainly in the problem gambling group (77.3%), other PGSI groups accounted for most of the more prevalent low (98.5%) and moderate (87.2%) harms reported. Proximal predictors of greater harm were use of online gambling and more frequent gambling on electronic gaming machines (EGMs), race betting sports betting, poker, skin gambling, scratchies, and loot box purchasing. Distal predictors were being younger, male, single, Aboriginal or Torres Strait Islander, and speaking a non-English language at home. At the population level, the greatest aggregate HRQoL impacts were amongst lower-risk gamblers, confirming the results of other studies regarding the 'prevention paradox'. Conclusions: The distribution of harm across gambler risk groups indicates the need for preventive measures, not just interventions for problem gambling. Reducing harm requires modifying product features that amplify their risk, especially for EGMs, race betting and sports betting that are both inherently risky and widely used. Gambling harm exacerbates health disparities for disadvantaged and vulnerable groups, requiring targeted resources and support.

The COVID-19 lockdown experience suggests that restricting the supply of gambling can reduce gambling problems: An Australian prospective study.

Background and aims: COVID-19 lockdowns limited access to gambling but simultaneously elevated psychosocial stressors. This study assessed the relative effects of these changes on gambling risk status during and after the Australian COVID-19 lockdown from late-March to late-May 2020. Methods: The study administered three surveys to people who had gambled within the past year at T1. Wave 1 asked about before (T1, N = 2,125) and during lockdown (T2, N = 2,125). Subsequent surveys focused on one year (T3; N = 649) and two years after lockdown (T4, N = 458). The dependent variable was changes in reporting any problem gambling symptoms (PGSI 0 vs 1+). Bivariate analyses and multinomial logistic regression tested for significant associations with: demographics, psychosocial stressors (perceived stress, psychological distress, loneliness, health anxiety about COVID, financial hardship, stressful life events), gambling participation and gambling frequency. Results: Gambling participation and at-risk gambling decreased between T1 and T2, increased at T3, with little further change at T4. When gambling availability was curtailed, decreased gambling frequency on EGMs, casino games, sports betting or race betting, and lower psychosocial stress, were associated with transitions from at-risk to non-problem gambling. When gambling availability resumed, increased EGM gambling frequency, decreased online gambling frequency, and higher psychosocial stress were associated with transitions from non-problem to at-risk gambling. Discussion and conclusions: Gambling availability appears a stronger influence on gambling problems, at the population level, than psychosocial risk factors. Reducing the supply of high-risk gambling products, particularly EGMs, is likely to reduce gambling harm.

Concise review: The Piwi-piRNA axis: pivotal beyond transposon silencing.

Piwi proteins and their associated piRNAs are essential for preserving the self-renewal property of mammalian germ stem cells. Their highly conserved role in CpG island DNA methylation and chromatin modifications in germ stem cells has long been associated with transposon silencing but recent reports hint at protein coding regions being targets for Piwi-mediated epigenetic changes as well. Interestingly, the expression of PIWI family members is not restricted to the germline, and certain members have also been implicated in tumorigenesis in cases of adenocarcinomas, gliomas, and sarcomas. The following review discusses our knowledge of the function of Piwi proteins and piRNAs in suppressing transposable elements while maintaining the self-renewing population of germ stem cells. We also highlight the somatic function of Piwi as an epigenetic modifier. Furthermore, we summarize the recently uncovered involvement of Piwi proteins and piRNAs in various cancers.

The vent-like homeobox gene VENTX promotes human myeloid differentiation and is highly expressed in acute myeloid leukemia.

Recent data indicate that a variety of regulatory molecules active in embryonic development may also play a role in the regulation of early hematopoiesis. Here we report that the human Vent-like homeobox gene VENTX, a putative homolog of the Xenopus xvent2 gene, is a unique regulatory hematopoietic gene that is aberrantly expressed in CD34(+) leukemic stem-cell candidates in human acute myeloid leukemia (AML). Quantitative RT-PCR documented expression of the gene in lineage positive hematopoietic subpopulations, with the highest expression in CD33(+) myeloid cells. Notably, expression levels of VENTX were negligible in normal CD34(+)/CD38(-) or CD34(+) human progenitor cells. In contrast to this, leukemic CD34(+)/CD38(-) cells from AML patients with translocation t(8,21) and normal karyotype displayed aberrantly high expression of VENTX. Gene expression and pathway analysis demonstrated that in normal CD34(+) cells enforced expression of VENTX initiates genes associated with myeloid development and down-regulates genes involved in early lymphoid development. Functional analyses confirmed that aberrant expression of VENTX in normal CD34(+) human progenitor cells perturbs normal hematopoietic development, promoting generation of myeloid cells and impairing generation of lymphoid cells in vitro and in vivo. Stable knockdown of VENTX expression inhibited the proliferation of human AML cell lines. Taken together, these data extend our insights into the function of embryonic mesodermal factors in human postnatal hematopoiesis and indicate a role for VENTX in normal and malignant myelopoiesis.

Simplified screening and referral protocol for sinonasal mucormycosis in post COVID-19 patients.

Background: To study incidence of sinonasal mucormycosis in active and post COVID-19 patients in a district-level hospital in India and develop a simplified screening and referral protocol for use at peripheral centres to aid rapid diagnosis/treatment. Methods: Study design: A prospective, interventional cohort study conducted from April 2021 to January 2022. Setting: Secondary level hospital in North India. Inclusion criteria: COVID-19 positive patients with diabetes mellitus as co-morbidity and with at least one of the following: received steroid therapy and/or on high flow oxygen therapy and/or had prolonged hospital stay (> 7 days). Exclusion criteria: Patients already immunocompromised/having malignancy/organ transplant recipients. Clinical workup: History, examination, imaging (CECT/MRI nose and paranasal sinuses if indicated), diagnostic nasal endoscopy + Nasal scrapings for KOH mount to detect fungal elements. STROBE guidelines were followed in the study. Results: Fourteen out of 250 patients tested positive for mucormycosis (incidence 5.6%). Thirteen were symptomatic, one patient was asymptomatic and detected on screening. No significant difference was found in mucormycosis versus non-mucormycosis group with respect to HbA1c status, vaccination status or steroid + oxygen treatment (p > 0.05 in all scenarios). Patients were treated with intravenous liposomal amphotericin B and surgical debridement when indicated. Two succumbed to disease (survival 85.7%). A clinical screening protocol was thus developed which can be used as an effective tool even at far-flung and remote healthcare facilities for diagnosis and timely referral of patients. Conclusions: Mucormycosis is a potentially lethal disease which needs rapid diagnosis and timely action to decrease morbidity and mortality.

Npm1 haploinsufficiency in collaboration with MEIS1 is sufficient to induce AML in mice.

NPM1 is among the most frequently mutated genes in acute myeloid leukemia (AML). Mutations in the NPM1 gene result in the increased export of NPM1 to the cytoplasm (NPM1c) and are associated with multiple transforming events including the aberrant upregulation of MEIS1 that maintains stem cell and cell cycle-associated pathways in NPM1c AML. However, another consequence of the NPM1c mutation is the inadequate levels of NPM1 wild-type in the nucleus and nucleolus, caused by the loss of one wild-type allele in addition to enforced NPM1 nuclear export. The contribution of NPM1 haploinsufficiency independently of the NPM1 mutation to AML development and its relationship with MEIS1 function is poorly understood. Using mouse models, our study shows that NPM1 haploinsufficiency paired with MEIS1 overexpression is sufficient to induce a fully penetrant AML in mice that transcriptionally resembles human NPM1c AML. NPM1 haploinsufficiency alters MEIS1-binding occupancies such that it binds the promoter of the oncogene structural maintenance of chromosome protein 4 (SMC4) in NPM1 haploinsufficient AML cells but not in NPM1 wild-type-harboring Hoxa9/Meis1-transformed cells. SMC4 is higher expressed in haploinsufficient and NPM1c+ AML cells, which are more vulnerable to the disruption of the MEIS1-SMC4 axis compared with AML cells with nonmutated NPM1. Taken together, our study underlines that NPM1 haploinsufficiency on its own is a key factor of myeloid leukemogenesis and characterizes the MEIS1-SMC4 axis as a potential therapeutic target in this AML subtype.

Electronic gaming machine accessibility and gambling problems: A natural policy experiment.

Background: Electronic gaming machines (EGMs) are one of the most harmful forms of gambling at an individual level. It is unclear whether restriction of EGM functions and accessibility results in meaningful reductions in population-level gambling harm. Methods: A natural policy experiment using a large (N = 15,000) national dataset weighted to standard population variables was employed to compare estimates of gambling problems between Australian residents in Western Australia (WA), where EGMs are restricted to one venue and have different structural features, to residents in other Australian jurisdictions where EGMs are widely accessible in casinos, hotels and clubs. Accessibility of other gambling forms is similar across jurisdictions. Results: Gambling participation was higher in WA, but EGM participation was approximately half that of the rest of Australia. Aggregate gambling problems and harm were about one-third lower in WA, and self-reported attribution of harm from EGMs by gamblers and affected others was 2.7× and 4× lower, respectively. Mediation analyses found that less frequent EGM use in WA accounted for the vast majority of the discrepancy in gambling problems (indirect path = -0.055, 95% CI -0.071; -0.038). Moderation analyses found that EGMs are the form most strongly associated with problems, and the strength of this relationship did not differ significantly across jurisdictions. Discussion: Lower harm from gambling in WA is attributable to restricted accessibility of EGMs, rather than different structural features. There appears to be little transfer of problems to other gambling forms. These results suggest that restricting the accessibility of EGMs substantially reduces gambling harm.

Outcome of simultaneous angioembolization and nephron sparing surgery in large renal angiomyolipomas.

AIM: To study the outcome of simultaneous angioembolization and nephron sparing surgery in large renal angiomyolipomas. MATERIALS AND METHODS: A prospective study of carried out from 2016 to 2019. A total of 15 patients were included in the study with a lesion (angiomyolipoma) more than 10 cm in size, suitable for nephron sparing surgery. The workup of the patients included history, baseline blood investigations, ultrasonography, and CT urography including angiographic films. All the patients were taken up for selective of angioembolization of the feeding vessels of the AML carried out by the interventional radiologist followed by nephron sparing surgery in the same sitting. The short term outcomes studied were warm ischemia time, average blood loss, and length of post-operative hospital stay. The oncological outcome was evaluated by noting the surgical margins of histopathological specimen and functional outcome by assessing the function of the preserved renal parenchyma. RESULTS: Twelve out of fifteen cases were female. The mean age was 42.25 years. All the patients had lesion more than 10 cm with seven tumors located at the lower pole, four at mid-pole, and four at upper pole. Eight patients had low complexity score on RENAL score (i.e. 4-6), five patients medium complexity score (i.e. 7-9), and two had high complexity score (i.e. ⩾10). Average blood loss was 200 ml, warm ischemia time was 18.46 min and postoperative stay was 3.55 days. All the 15 specimens sent for histopathology were confirmed as AML (angiomyolipomas) with margins free of tumor. Follow up CECT done at 4 months postoperatively revealed functioning residual renal parenchyma with prompt excretion of contrast. CONCLUSION: Large AML's are also amenable to nephron sparing surgery. However patient should always be warned about the possibility of total nephrectomy. Selective angioembolization helps in reducing the blood supply and risk of torrential bleeding thus facilitates in the removal of the tumor and increasing the chances of nephron sparing surgery.