Impact of Operative Approach on Acute Kidney Injury Risk Prediction Models for Colectomy.

INTRODUCTION: Acute kidney injury (AKI) is a serious postoperative complication associated with increased morbidity and mortality. Identifying patients at risk for AKI is important for risk stratification and management. This study aimed to develop an AKI risk prediction model for colectomy and determine if the operative approach (laparoscopic versus open) alters the influence of predictive factors through an interaction term analysis. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was analyzed from 2005 to 2019. Patients undergoing laparoscopic and open colectomy were identified and propensity score matched. Multivariable logistic regression identified significant preoperative demographic, comorbidity, and laboratory value predictors of AKI. The predictive ability of a baseline model consisting of these variables was compared to a proposed model incorporating interaction terms between operative approach and predictor variables using the likelihood ratio test, c-statistic, and Brier score. Shapley Additive Explanations values assessed relative importance of significant predictors. RESULTS: 252,372 patients were included in the analysis. Significant AKI predictors were hypertension, age, sex, race, body mass index, smoking, diabetes, preoperative sepsis, Congestive heart failure, preoperative creatinine, preoperative albumin, and operative approach (P < 0.001). The proposed model with interaction terms had improved predictive ability per the likelihood ratio test (P < 0.05) but had no statistically significant interaction terms. C-statistic and Brier scores did not improve. Shapley Additive Explanations analysis showed hypertension had the highest importance. The importance of age and diabetes showed some variation between operative approaches. CONCLUSIONS: While the inclusion of interaction terms collectively improved AKI prediction, no individual operative approach interaction terms were significant. Including operative approach interactions may enhance predictive ability of AKI risk models for colectomy.

Tumor differentiation impacts response to neoadjuvant therapy and survival in patients with esophageal adenocarcinoma.

OBJECTIVE: The current staging system for esophageal adenocarcinoma only considers tumor grade in early tumors. The aim of this study was to evaluate the impact of tumor differentiation on response to neoadjuvant chemoradiotherapy and survival in patients with locally advanced esophageal adenocarcinoma. METHODS: This was a multi-institution retrospective review of all patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy followed by esophagectomy from January 2010 to December 2017. Response to neoadjuvant therapy and survival was compared between patients with well- or moderately differentiated (G1/2) tumors versus poorly differentiated (G3) tumors. RESULTS: There were 550 patients, 485 men (88.2%) and 65 women. The median age was 61 years, and the tumor was G1/2 in 288 (52.4%) and G3 in 262 patients. Overall clinical stage before neoadjuvant therapy was similar between groups. Pathologic complete response (pCR) was found in 87 patients (15.8%). The frequency of pCR was similar between groups, but residual disease in the esophagus and lymph nodes was significantly more likely with G3 tumors. Median follow-up was 63 months and absolute survival, overall survival, and disease-free survival were all significantly worse in patients with G3 tumors. Further, even with pCR, patients with G3 tumors had significantly worse survival. CONCLUSIONS: This study showed that response to neoadjuvant therapy was not affected by tumor differentiation. However, poor differentiation was associated with worse survival compared with patients with G1/2 tumors, even among those with pCR. These results suggest that poor differentiation should be considered as an added risk factor for clinical staging in patients with locally advanced esophageal adenocarcinoma.

Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma.

Background Abbreviated MRI is a proposed paradigm shift for hepatocellular carcinoma (HCC) surveillance, but data on its performance are lacking for histopathologically confirmed early-stage HCC. Purpose To evaluate the sensitivity and specificity of dynamic contrast-enhanced abbreviated MRI for early-stage HCC detection, using surgical pathologic findings as the reference standard. Materials and Methods This retrospective study was conducted at three U.S. liver transplant centers in patients with cirrhosis who underwent liver resection or transplant between January 2009 and December 2019 and standard "full" liver MRI with and without contrast enhancement within 3 months before surgery. Patients who had HCC-directed treatment before surgery were excluded. Dynamic abbreviated MRI examinations were simulated from the presurgical full MRI by selecting the coronal T2-weighted and axial three-dimensional fat-suppressed T1-weighted dynamic contrast-enhanced sequences at precontrast, late arterial, portal venous, and delayed phases. Two abdominal radiologists at each center independently interpreted the simulated abbreviated examinations with use of the Liver Imaging Reporting and Data System version 2018. Patients with any high-risk liver observations (>LR-3) were classified as positive; otherwise, they were classified as negative. With liver pathologic findings as the reference standard for the presence versus absence of early-stage HCC, the sensitivity, specificity, and their 95% CIs were calculated. Logistic regression was used to identify factors associated with correct classification. Results A total of 161 patients with early-stage HCC (median age, 62 years [IQR, 58-67 years]; 123 men) and 138 patients without HCC (median age, 55 years [IQR, 47-63 years]; 85 men) were confirmed with surgical pathologic findings. The sensitivity and specificity of abbreviated MRI were 88.2% (142 of 161 patients) (95% CI: 83.5, 92.5) and 89.1% (123 of 138 patients) (95% CI: 84.4, 93.8), respectively. Sensitivity was lower for Child-Pugh class B or C versus Child-Pugh class A cirrhosis (64.1% vs 94.2%; P < .001). Conclusion With surgical pathologic findings as the reference standard, dynamic abbreviated MRI had high sensitivity and specificity for early-stage hepatocellular carcinoma detection in patients with compensated cirrhosis but lower sensitivity in those with decompensated cirrhosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim in this issue.

Correlation of LI-RADS 3 or 4 Observations with Histopathologic Diagnosis in Patients with Cirrhosis.

Patients with cirrhosis are high risk for developing hepatocellular carcinoma (HCC) and warrant surveillance using abdominal ultrasound and α-fetoprotein.1 Those with positive surveillance results should undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI). The LI-RADS system is an evidence-based system to classify observations on CT or MRI in at-risk patients, ranging from LR-1 (definite benign) to LR-5 (definite HCC), with LR-3 and LR-4 observations being intermediate risk for HCC.2 LR-3 and LR-4 observations are observed on CT or MRI in more than one-fourth of patients undergoing HCC surveillance and have a high, yet variable, risk for progression to HCC.3 Approximately one-third of patients with LR-3 observations and more than two-thirds of LR-4 observations develop HCC, and surveillance strategies vary widely in practice.4,5 Variation in radiographic appearance and natural history of these observations suggests that this may be a heterogeneous group of patients; however, their histopathology has not been well described. Herein, we correlated imaging findings and explant histopathology from liver transplant recipients with at least 1 LR-3 or LR-4 observation on CT or MRI within 6 months preceding transplantation.

The Impact of Ineffective Esophageal Motility on Patients Undergoing Magnetic Sphincter Augmentation.

OBJECTIVE: To evaluate and characterize outcomes of MSA in patients with IEM. SUMMARY BACKGROUND DATA: MSA improves patients with gastroesophageal reflux and normal motility. However, many patients have IEM, which could impact the outcomes of MSA and discourage use. METHODS: An international, multi-institutional case control study of IEM patients undergoing MSA matched to normal patients was performed. Primary outcomes were new onset dysphagia and need for postoperative interventions. RESULTS: A total of 105 IEM patients underwent MSA with matching controls. At 1 year after MSA: GERD-Health Related Quality of Life was similar; DeMeester scores in IEM patients improved to 15.7 and 8.5 in controls ( P = 0.021); and normalization of the DeMeester score for IEM = 61.7% and controls = 73.1% ( P = 0.079).In IEM patients, 10/12 (83%) with preop dysphagia had resolution; 11/66 (17%) had new onset dysphagia and 55/66 (83%) never had dysphagia. Comparatively, in non-IEM patients, 22/24 (92%) had dysphagia resolve; 2/24 (8%) had persistent dysphagia; 7/69 (10%) had new onset dysphagia, and 62/69 (90%) never had dysphagia.Overall, 19 (18%) IEM patients were dilated after MSA, whereas 12 (11%) non-IEM patients underwent dilation ( P = 0.151). Nine (9%) patients in both groups had their device explanted. CONCLUSIONS: Patients with IEM undergoing MSA demonstrate improved quality of life and reduction in acid exposure. Key differences in IEM patients include lower rates of objective GERD resolution, lower resolution of existing dysphagia, higher rates of new onset dysphagia and need for dilation. GERD patients with IEM should be counselled about these possibilities.

Long-term clinical and functional results of magnetic sphincter augmentation.

Magnetic sphincter augmentation (MSA) was introduced in 2007 as an alternative surgical procedure for patients with gastroesophageal reflux disease (GERD). The majority of data since MSA's introduction has focused on short and intermediate-term results, demonstrating safety and high efficacy in terms of reflux symptom control, freedom from proton pump inhibitor use and normalization of distal esophageal acid exposure. However, GERD is a chronic condition that demands a long-term solution. Limited available data from studies reporting outcomes at 5 years or later following MSA demonstrate that the promising short- and mid-term efficacy and safety profile of MSA remains relatively constant in the long term. Compared with Nissen fundoplication, MSA has a much lower rate of gas-bloat and inability to belch at a short-term follow-up, a difference that persists in the long-term. The most common complaint after MSA at a short-term follow-up is dysphagia. However, limited data suggest dysphagia rates largely decrease by 5 years. Dysphagia is the most common indication for dilation and device removal in both early- and long-term studies. However, the overall rates of dilation and removal are similar in short- and long-term reports, suggesting the majority of these procedures are performed in the short-term period after device implantation. The indications and standard practices of MSA have evolved over time. Long-term outcome data currently available are all from patient cohorts who were selected for MSA under early restricted indications and outdated regimens. Therefore, further long-term studies are needed to corroborate the preliminary, yet encouraging long-term results.

Less is more: cruroplasty alone is sufficient for revisional hiatal hernia surgery.

BACKGROUND: Recurrence of hiatal hernia after anti-reflux surgery is common, with past studies reporting recurrence rates of 10-15%. Most patients experience relief from GERD symptoms following initial repair; however, those suffering from recurrence can have symptoms severe enough to warrant another operation. Although the standard of care is to revise the fundoplication or convert to magnetic sphincter augmentation (MSA) in addition to redo cruroplasty, it stands to reason that with an intact fundoplication, a repeat cruroplasty is all that is necessary to alleviate the patients' symptoms. In other words, only fix that which is broken. METHODS: A retrospective review of patients with symptomatic hiatal hernia recurrence who underwent reoperation between January 2011 and September 2018 was conducted. Patients who received revisional cruroplasty alone were compared with cruroplasty plus some other revision (fundoplication revision, or takedown and MSA placement). Demographics, operative details, and postoperative outcomes were collected. RESULTS: There were 73 patients identified. Median time to recurrence after the first procedure was 3.7 (1.9-8.2) years. Thirty-two percent of the patients had GERD symptoms for more than 10 years. Twenty-six patients underwent cruroplasty only. Forty-seven patients underwent cruroplasty plus fundoplication revision. There were no significant differences in operative times (2.4 h cruroplasty alone, 2.8 h full revision, p = 0.75) or postoperative complications between the two groups. Patients had a mean follow-up time of 1.64 years. Of the 73 patients, 8 had subsequent hiatal hernia recurrence. The recurrence rate for patients with cruroplasty alone was 11%, and the recurrence rate for the full revision group was 12% (p = 1.00). CONCLUSION: Leaving an intact fundoplication alone at the time of revisional surgery did not adversely affect surgical outcomes. This data suggests a role for hernia-only repair for recurrent hiatal hernias.

Regression of Barrett's esophagus after magnetic sphincter augmentation: intermediate-term results.

BACKGROUND: Untreated gastroesophageal reflux disease (GERD) can lead to Barrett's esophagus and an increased risk for esophageal adenocarcinoma. Magnetic sphincter augmentation (MSA) is a safe and effective modality for the treatment of GERD. Preliminary research on short-term outcomes after MSA demonstrated significant regression of Barrett's. Further investigation is required to evaluate the long-term effect of this treatment. METHODS: A retrospective review of patients was conducted with biopsy-proven Barrett's esophagus who underwent MSA between 2007 and 2019. As a part of their preoperative evaluation, patients underwent esophagogastroduodenoscopy (EGD) with biopsies of the distal esophagus and gastroesophageal junction including any abnormal-appearing segments, pH testing, and a videoesophagram. Patients were categorized according to the length of Barrett's identified (ultrashort < 1 cm, short 1-3 cm, long > 3 cm). Improvement was defined as a decrease in length (e.g. long to short). RESULTS: There were 87 patients identified for study inclusion. 55 patients were male. The median body mass index was 26.95. The median age was 61.81 (49.79-68.29). Mean follow-up time was 2.35 ± (1.57) years. 7 (8.0%) of these patients began with long segment Barrett's, 58 (66.7%) began with short segment disease, and 22 (25.3%) began with an ultrashort segment. Within this cohort, 74 (85.06%) had undergone postoperative biopsy. 7 out of 74 patients (9.46%) showed improvement in their intestinal metaplasia and 45/74 (60.81%) showed complete regression. Fisher's exact test showed a significant decrease in Barrett's length following MSA (p = 0.002). No patients progressed to dysplasia or neoplasia. There was a statistically significant decrease in the median Demeester score from 34.00 to 13.70 after surgery (p < .001). CONCLUSION: MSA reduces esophageal acid exposure and can lead to reduction or resolution of Barrett's esophagus. MSA is also effective at preventing progression of metaplasia to dysplasia or neoplasia. This effect remains consistent even after 2 years of follow-up.

Magnetic sphincter augmentation with hiatal hernia repair: long term outcomes.

INTRODUCTION: Magnetic sphincter augmentation (MSA) is a safe and effective treatment for patients with gastroesophageal reflux disease (GERD). MSA was initially indicated for patients with GERD and concomitant hiatal hernias < 3 cm. However, excellent short- and intermediate-term outcomes following MSA and hiatal hernia repair in patients with hiatal hernias ≥ 3 cm have been reported. The purpose of this study is to assess long-term outcomes for this patient population. METHODS AND PROCEDURES: A retrospective review was performed of patients with GERD and hiatal hernias ≥ 3 cm who underwent MSA and hiatal hernia repair. Patients were treated at two tertiary medical centers between May 2009 and December 2016. Follow up included annual video esophagram, upper endoscopy, or both. Outcomes included pre- and post-operative GERD health-related quality of life (GERD-HRQL) scores, length and regression of Barrett's esophagus, resolution of esophagitis, need for endoscopic dilations or implant removal, and clinically significant hiatal hernia recurrence (> 2 cm) on videoesophagram or endoscopy. RESULTS: Seventy-nine patients (53% female) with a median age of 65.56 (58.42-69.80) years were included. Median follow up was 2.98 (interquartile range 1.90-3.32) years. Median DeMeester scores decreased from 42.45 (29.12-60.73) to 9.10 (3.05-24.30) (p < 0.001). Severity of esophagitis (e.g. LA class C to class B) significantly improved (p < 0.01). Forty percent of patients with Barrett's esophagus experienced regression (p < 0.01). Median GERD-HRQL scores improved from 21 to 2. Five (6.3%) hiatal hernia recurrences occurred, and 1 required re-operation. Age, body mass index, size of the initial hiatal hernia, and sex had no significant effect on whether a patient developed a recurrence. CONCLUSIONS: Magnetic sphincter augmentation in conjunction with large hiatal hernia repairs for patients with GERD achieves excellent long-term radiographic and clinical results, and a low overall need for reoperation, without the need for mesh.

Magnetic sphincter augmentation versus fundoplication for gastroesophageal reflux disease: pros and cons.

PURPOSE OF REVIEW: The purpose of this magnetic sphincter augmentation (MSA) year in review article is to provide a clear understanding for the current state of MSA literature in 2019, and contrast MSA outcomes with traditional fundoplication. RECENT FINDINGS: Continued work was performed in 2019 to expand patient populations eligible for MSA including those with hiatal hernia, post-bariatric patients, patients necessitating a thoracic approach, and patients with esophageal intestinal metaplasia. Additionally, a large systematic review reinforced earlier findings comparing laparoscopic fundoplication to MSA. This study demonstrated equivalency over many different operative outcomes, with MSA patients having less bloating while also retaining the ability to belch and vomit. Furthermore, independent research teams found a modest cost savings for MSA over laparoscopic fundoplication with budget analysis. SUMMARY: MSA is a safe and efficacious procedure originally approved for patients with medically refractory, uncomplicated gastroesophageal reflux disease. The accumulating body of evidence suggests patients with intestinal metaplasia or hiatal hernias can safely and effectively undergo MSA, whereas further research will be required before MSA is widely used for post-bariatric patients or for patients requiring a transthoracic surgical approach. MSA is equivalent or superior to laparoscopic fundoplication in all surgical outcomes measured thus far.

Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease.

Magnetic sphincter augmentation is an effective and safe surgical method for the treatment of gastroesophageal reflux disease (GERD). The device has been compared with twice-daily proton pump inhibitor therapy and laparoscopic fundoplication (in randomized trials and prospective cohort studies, respectively). Magnetic sphincter augmentation was superior to medical therapy and equivalent to surgery for the relief of GERD symptoms. Recent research focuses on implanting the device into more complex patients, such as those with larger hiatal hernias or those with Barrett's esophagus. Additional novel research topics include cost analysis and predicting and minimizing postoperative dysphagia.

Recent progress in mapping the emerging landscape of the small-cell lung cancer genome.

Small-cell lung cancer (SCLC) remains the deadliest of all the lung cancer types. Its high mortality is largely attributed to the invariable development of resistance to standard chemo/radiotherapies, which have remained unchanged for the past 30 years, underscoring the need for new therapeutic approaches. The discovery of molecular targets for chemoprevention and treatment has been hampered by the poor understanding of SCLC progression. In recent years, comprehensive omics-based analyses have led to the discovery of recurrent alterations in patient tumors, and functional studies using genetically engineered mouse models and patient-derived tumor models have provided information about the alterations critical for SCLC pathogenesis. Defining the somatic alterations scattered throughout the SCLC genome will help to understand the underlying mechanism of this devastating disease and pave the way for the discovery of therapeutic vulnerabilities associated with the genomic alterations.

Comparing the Predictive Power of Preoperative Risk Assessment Tools to Best Predict Major Adverse Cardiac Events in Kidney Transplant Patients.

BACKGROUND: Patients undergoing kidney transplantation have increased risk of adverse cardiovascular events due to histories of hypertension, end-stage renal disease, and dialysis. As such, they are especially in need of accurate preoperative risk assessment. METHODS: We compared three different risk assessment models for their ability to predict major adverse cardiac events at 30 days and 1 year after transplant. These were the PORT model, the RCRI model, and the Gupta model. We used a method based on generalized U-statistics to determine statistically significant improvements in the area under the receiver operator curve (AUC), based on a common major adverse cardiac event (MACE) definition. For the top-performing model, we added new covariates into multivariable logistic regression in an attempt to create further improvement in the AUC. RESULTS: The AUCs for MACE at 30 days and 1 year were 0.645 and 0.650 (PORT), 0.633 and 0.661 (RCRI), and finally 0.489 and 0.557 (Gupta), respectively. The PORT model performed significantly better than the Gupta model at 1 year (p=0.039). When the sensitivity was set to 95%, PORT had a significantly higher specificity of 0.227 compared to RCRI's 0.071 (p=0.009) and Gupta's 0.08 (p=0.017). Our additional covariates increased the receiver operator curve from 0.664 to 0.703, but this did not reach statistical significance (p=0.278). CONCLUSIONS: Of the three calculators, PORT performed best when the sensitivity was set at a clinically relevant level. This is likely due to the unique variables the PORT model uses, which are specific to transplant patients.

Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition.

CREBBP, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon Crebbp inactivation in an autochthonous mouse model. Extending these observations beyond the lung, broad Crebbp deletion in mouse neuroendocrine cells cooperated with Rb1/Trp53 loss to promote neuroendocrine thyroid and pituitary carcinomas. Gene expression analyses showed that Crebbp loss results in reduced expression of tight junction and cell adhesion genes, including Cdh1, across neuroendocrine tumor types, whereas suppression of Cdh1 promoted transformation in SCLC. CDH1 and other adhesion genes exhibited reduced histone acetylation with Crebbp inactivation. Treatment with the histone deacetylase (HDAC) inhibitor Pracinostat increased histone acetylation and restored CDH1 expression. In addition, a subset of Rb1/Trp53/Crebbp-deficient SCLC exhibited exceptional responses to Pracinostat in vivo Thus, CREBBP acts as a potent tumor suppressor in SCLC, and inactivation of CREBBP enhances responses to a targeted therapy.Significance: Our findings demonstrate that CREBBP loss in SCLC reduces histone acetylation and transcription of cellular adhesion genes, while driving tumorigenesis. These effects can be partially restored by HDAC inhibition, which exhibited enhanced effectiveness in Crebbp-deleted tumors. These data provide a rationale for selectively treating CREBBP-mutant SCLC with HDAC inhibitors. Cancer Discov; 8(11); 1422-37. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1333.

Transcriptional deregulation underlying the pathogenesis of small cell lung cancer.

The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development. It will also describe the roles of lineage-specific factors in neuroendocrine (NE) cell differentiation and homeostasis and the roles of epigenetic alterations driven by changes in NFIB and chromatin modifiers in malignant progression and chemoresistance. These recent findings have led to a model of transcriptional network in which multiple pathways converge on regulatory regions of crucial genes linked to tumor development. Validation of this model and characterization of target genes will provide critical insights into the biology of SCLC and novel strategies for tumor intervention.

A Retrospective Cohort Study on Rehospitalization following Expanded Criteria Donor Kidney Transplantation.

BACKGROUND: Expanded criteria donor (ECD) kidneys are commonly used but are associated with increased graft failure. Graft failure is in turn related to rehospitalization within thirty days post transplant. Our goal was to determine whether ECD kidneys independently lead to rehospitalization within 30 days, 1 year, and 2 years after transplant. METHODS: All adult first-time recipients of deceased donor kidneys transplanted from 2003-2012 at our center were reviewed. Models included demographics, medical comorbidities, center for disease control high-risk kidney, ECD kidney, ischemia times, cause of renal failure, immunosuppressive regimen, positive psychiatric screening, alcoholism, surgeon, year the transplant was performed, years on dialysis before transplant, and the number of inpatient hospitalizations within 6 months prior to transplant. We conducted Andersen-Gill modeling and propensity score matching followed by logistic regression. We also used multivariable linear regression to predict average length of stay during rehospitalization. RESULTS: More ECD patients had a rehospitalization at 1 year (70.3% versus 59%, log-rank test p=0.014). Thirty-day and 2-year time marks were not significant. Andersen-Gill models predicting successive hospitalizations yielded HR of 1.42 (p=0.002) and 1.32 (p=0.015) for ECD patients at 1 and 2 years of after transplantation, respectively. Propensity score matching and logistic regression showed a significant relative risk of 1.630 at one year (p=0.033) and 1.313 at two years (p=0.268). There was no significant association between ECD and subsequent lengths of hospital stay. CONCLUSION: Receiving an ECD kidney is independently associated with multiple readmissions within 2 years of transplant but unrelated to length of stay.

Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer.

Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma. MYCL (L-Myc) is frequently amplified in human SCLC, but its roles in SCLC progression are poorly understood. We isolated preneoplastic neuroendocrine cells from a mouse model of SCLC and found that ectopic expression of L-Myc, c-Myc, or N-Myc conferred tumor-forming capacity. We focused on L-Myc, which promoted pre-rRNA synthesis and transcriptional programs associated with ribosomal biogenesis. Deletion of Mycl in two genetically engineered models of SCLC resulted in strong suppression of SCLC. The high degree of suppression suggested that L-Myc may constitute a therapeutic target for a broad subset of SCLC. We then used an RNA polymerase I inhibitor to target rRNA synthesis in an autochthonous Rb/p53-deleted mouse SCLC model and found significant tumor inhibition. These data reveal that activation of RNA polymerase I by L-Myc and other MYC family proteins provides an axis of vulnerability for this recalcitrant cancer.

Uranium, thorium and rare earth elements in macrofungi: what are the genuine concentrations?

Concentrations of uranium, thorium and rare earth elements (REE) in 36 species of ectomycorrhizal (26 samples) and saprobic (25 samples) macrofungi from unpolluted sites with differing bedrock geochemistry were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Analytical results are supported by use of certified reference materials (BCR-670, BCR-667, NIST-1575a) and the reliability of the determination of uranium was verified by epithermal neutron activation analysis (ENAA). It appears that data recently published on these elements are erroneous, in part because of use of an inappropriate analytical method; and in part because of apparent contamination by soil particles resulting in elevated levels of thorium and REE. Macrofungi from unpolluted areas, in general, did not accumulate high levels of the investigated metals. Concentrations of uranium and thorium were generally below 30 and 125 µg kg(-1) (dry weight), respectively. Concentrations of REE in macrofungi did not exceed 360 µg kg(-1) (dry weight) and their distribution more or less followed the trend observed in post-Archean shales and loess.