Publications by authors named "Carolyn Glass"

34 Publications

SMARCA4 and other SWI/SNF family genomic alterations in non-small cell lung cancer: Clinicopathological characteristics and outcomes to immune checkpoint inhibition.

J Thorac Oncol 2021 Apr 9. Epub 2021 Apr 9.

Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA. Electronic address:

Introduction: The SWI/SNF (SWitch/Sucrose Non-Fermentable) chromatin remodeling complex acts as a regulatory component of transcription, and inactivating mutations within the complex are implicated in genomic instability, higher tumor mutational burden (TMB), and an aggressive cancer phenotype. Whether SMARCA4 and other SWI/SNF alterations are independent prognostic factors or associated with clinical outcomes to immune checkpoint inhibitors (ICIs) in NSCLC remains unclear.

Methods: We collected clinicopathologic and genomic data from patients with NSCLC that underwent targeted next-generation sequencing (NGS) at the Dana-Farber Cancer Institute. Tumors were characterized based on the presence or absence of mutations across a set of 6 SWI/SNF genes (ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1).

Results: Of 2689 patients with NSCLC, 20.6% (N=555) had SWI/SNF genomic alterations. Compared to SWI/SNF wild-type (wt) NSCLC, patients with SWI/SNF mutant NSCLCs had a lower prevalence of concurrent targetable driver mutations (33.2% vs 22.2%; P<0.001), a higher TMB (median 8.5 vs 12.2 mutations/megabase; P<0.001), a shorter median overall survival (mOS) from the time of advanced disease diagnosis (25.0 vs 19.3 months; P=0.01); the detrimental effect in OS appeared to be largely driven by SMARCA4 mutations (mOS: 25.0 months for SMARCA4 wt vs 15.6 months for SMARCA4 mutant; P<0.001). Among 532 patients who received ICIs, 25.5% (N=136) harbored SWI/SNF mutations. From the start of immunotherapy, there was no difference in objective response rate (ORR 19.9% vs 25.0%; P=0.2), median progression-free survival (mPFS 3.0 vs 3.0 months; HR: 0.96 [95% CI: 0.77-1.18]; P=0.7), or mOS (13.1 vs 9.5 months; HR: 0.81 [95% CI: 0.64-1.02]; P=0.07) in SWI/SNF wt vs SWI/SNF mutant NSCLC, respectively. However, among KRAS-mutant NSCLCs treated with ICIs (N=176), a concurrent SWI/SNF mutation (N=39) conferred a numerically lower ORR (21.9% vs 12.8%; P=0.2), a significantly shorter mPFS (4.1 vs 1.8 months; HR: 0.57 [95%CI: 0.38-0.84]; P=0.005), and a significantly shorter mOS (15.5 vs 8.2 months; HR: 0.56 [95%CI: 0.36-0.86]; P=0.008). The deleterious effect on immunotherapy outcomes in KRAS-mutant NSCLC was most pronounced in the SMARCA4-mutant subset (N=17), with a lower ORR (22% vs 0%, P=0.03) a significantly shorter mPFS (4.1 vs 1.4 months; HR: 0.25 [95%CI: 0.14-0.42]; P<0.001), and a significantly shorter mOS (15.1 vs 3.0 months; HR: 0.29 [95%CI: 0.17-0.50]; P<0.001) compared to SMARCA4-wt KRAS-mutant NSCLCs.

Conclusions: Although there were no significant associations between SWI/SNF mutation status and immunotherapy efficacy in the overall NSCLC cohort, the presence of a SMARCA4 alteration may confer a worse outcome to immunotherapy among KRAS-mutant NSCLCs.
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http://dx.doi.org/10.1016/j.jtho.2021.03.024DOI Listing
April 2021

PD-1 and PD-L1 Expression in Cardiac Transplantation.

Cardiovasc Pathol 2021 Mar 15:107331. Epub 2021 Mar 15.

Department of Pathology, Duke University, Durham NC; Duke Transplant Center, Duke University, Durham NC. Electronic address:

Programmed death-ligand 1 (PD-L1), a transmembrane protein and member of the CD28 T cell family is associated with lymphocyte activation. PD-L1 expression is upregulated on activated antigen presenting cells such as monocytes, myeloid and dendritic cells. When bound to its cognate receptor programmed cell death (PD-1), inhibition of immune responses including downregulation of T cell proliferation occurs. Mechanistically, such inhibition would be hypothetically favorable in the setting of a transplanted organ undergoing allograft rejection. However, there is a paucity of data addressing the role of PD-L1 and PD-1 expression in the human transplanted heart.
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http://dx.doi.org/10.1016/j.carpath.2021.107331DOI Listing
March 2021

Potentially functional variants of ERAP1, PSMF1 and NCF2 in the MHC-I-related pathway predict non-small cell lung cancer survival.

Cancer Immunol Immunother 2021 Mar 2. Epub 2021 Mar 2.

Duke University Medical Center and Department of Population Health Sciences, Duke Cancer Institute, Duke University School of Medicine, 905 S LaSalle Street, Durham, NC, 27710, USA.

Background: Cellular immunity against tumor cells is highly dependent on antigen presentation by major histocompatibility complex class I (MHC-I) molecules. However, few published studies have investigated associations between functional variants of MHC-I-related genes and clinical outcomes of lung cancer patients.

Methods: We performed a two-phase Cox proportional hazards regression analysis by using two previously published genome-wide association studies to evaluate associations between genetic variants in the MHC-I-related gene set and the survival of non-small cell lung cancer (NSCLC) patients, followed by expression quantitative trait loci analysis.

Results: Of the 7811 single-nucleotide polymorphisms (SNPs) in 89 genes of 1185 NSCLC patients in the discovery dataset of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 24 SNPs remained statistically significant after validation in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. In a multivariate stepwise Cox model, three independent functional SNPs (ERAP1 rs469783 T > C, PSMF1 rs13040574 C > A and NCF2 rs36071574 G > A) remained significant with an adjusted hazards ratio (HR) of 0.83 [95% confidence interval (CI) = 0.77-0.89, P = 8.0 × 10], 0.86 (0.80-0.93, P = 9.4 × 10) and 1.31 (1.11-1.54, P = 0.001) for overall survival (OS), respectively. Further combined genotypes revealed a poor survival in a dose-response manner in association with the number of unfavorable genotypes (P < 0.0001 and 0.0002 for OS and disease-specific survival, respectively). Also, ERAP1 rs469783C and PSMF1 rs13040574A alleles were associated with higher mRNA expression levels of their genes.

Conclusion: These potentially functional SNPs of the MHC-I-related genes may be biomarkers for NSCLC survival, possibly through modulating the expression of corresponding genes.
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http://dx.doi.org/10.1007/s00262-021-02877-9DOI Listing
March 2021

Potentially functional variants of HBEGF and ITPR3 in GnRH signaling pathway genes predict survival of non-small cell lung cancer patients.

Transl Res 2021 Jan 2. Epub 2021 Jan 2.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina; Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North Carolina. Electronic address:

The gonadotropin-releasing hormone (GnRH) signaling pathway controls reproductive functions and cancer growth and progression. However, few studies investigated roles of genetic variants of GnRH pathway genes in survival of patients with non-small cell lung cancer (NSCLC). Therefore, we first evaluated associations between 22,528 single-nucleotide polymorphisms (SNPs) in 101 GnRH pathway genes and survival of 1185 NSCLC patients using a dataset from Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We found 572 SNPs to be significantly associated with overall survival (OS) of NSCLC (P ≤ 0.05, Bayesian false discovery probability ≤0.80). We then validated these SNPs in another dataset with 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study. Finally, two independent SNPs (HBEGF rs4150236G>A and ITPR3 rs116454384C>T) remained significantly associated with NSCLC OS in the combined analysis with hazards ratios of 0.84 (95% confidence interval = 0.76-0.92, P = 0.0003) and 0.85 (0.78-0.94, 0.0012), respectively; their genetic score (the number of protective genotypes) was associated with a better OS and disease-specific survival (P = 0.0002 and 0.0001, respectively). Further expression quantitative trail loci analysis showed a significant correlation between ITPR3 rs116454384 T allele and an increased mRNA expression level in both whole blood and normal lung tissue, and high ITPR3 mRNA expression levels in tumors were associated with a better survival of NSCLC patients. Because ITPR3 mutations were rare in tumors, ITPR3 rs116454384C>T likely had an effect on cancer progression by regulating the gene expression. Therefore, genetic variants of HBEGF rs4150236G>A and ITPR3 rs116454384C>T may be predictors for NSCLC survival, but HBEGF rs4150236G>A functional relevance remains to be determined.
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http://dx.doi.org/10.1016/j.trsl.2020.12.009DOI Listing
January 2021

Novel genetic variants of and related lymphangiogenesis signaling pathway predict non-small cell lung cancer survival.

Am J Cancer Res 2020 1;10(8):2603-2616. Epub 2020 Aug 1.

Duke Cancer Institute, Duke University Medical Center Durham, NC 27710, USA.

Although lymphangiogenesis is a vital step in lung cancer metastasis, the association between lymphangiogenesis and non-small cell lung cancer (NSCLC) survival remains unclear. Since single-nucleotide polymorphisms (SNPs) have been reported to predict NSCLC survival, we investigated associations between SNPs in lymphangiogenesis-related pathway genes and NSCLC survival in a discovery genotyping dataset of 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another genotyping dataset of 984 patients from the Harvard Lung Cancer Susceptibility Study. We evaluated associations between 34,509 genetic variants (3252 genotyped and 31,257 imputed) in 247 genes involved in lymphangiogenesis-related pathway and NSCLC survival. After validation, we finally identified two independent SNPs ( rs11787670 A>G and rs67715745 T>C) to be significantly associated with NSCLC overall survival (OS), with adjusted hazards ratios of 0.77 and 0.83 (95% confidence interval =0.66-0.90, =7.20×10) and 0.84 (95% confidence interval =0.75-0.92, =3.50×10), respectively. Moreover, an increasing number of combined protective alleles of these two SNPs was significantly associated with an improved NSCLC OS and disease-specific survival (DSS) in the PLCO dataset (=0.011 and 0.006, respectively). Furthermore, the addition of these protective alleles to the prediction model for the 5-year survival increased the time-dependent area under the curve both from 87% to 87.67% for OS (=0.029) and from 88.54% to 89.06% for DSS (=0.022). Subsequent expression quantitative trait loci (eQTL) functional analysis revealed that the rs11787670 G allele was significantly associated with an elevated mRNA expression in normal tissues. Additional analyses suggested a suppressor role for both and in NSCLC survival. Collectively, these findings indicated that rs11787670 A>G and rs67715745 T>C may be independent prognostic factors for NSCLC survival once further validated.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471352PMC
August 2020

Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters.

Am J Surg Pathol 2021 02;45(2):255-262

Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ.

Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.
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http://dx.doi.org/10.1097/PAS.0000000000001574DOI Listing
February 2021

Novel genetic variants of and involved in immunoregulatory interactions are associated with non-small cell lung cancer survival.

Am J Cancer Res 2020 1;10(6):1770-1784. Epub 2020 Jun 1.

Duke Cancer Institute, Duke University Medical Center Durham, NC 27710, USA.

Immunoregulatory interactions play a pivotal role in immune surveillance, recognition, and killing, particularly its internal pathway, likely playing an important role in immune escape. By using two genotyping datasets, one from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer screening trial (n = 1,185) as the discovery, and the other from Harvard Lung Cancer Susceptibility (HLCS) study (n = 984) as the validation, we evaluated associations between 4,713 genetic variants (338 genotyped and 4,375 imputed) in 60 genes involved in immunoregulatory interactions and survival of non-small cell lung cancer (NSCLC). We found that 115 SNPs were significantly associated with NSCLC overall survival in the discovery, of which four remained significant after validation by the HLCS dataset after multiple test correction by Bayesian false discovery probability. Final combined analysis identified two independent SNPs ( rs4487030 A>G and rs35385129 C>A) that predicted NSCLC survival with a combined hazards ratio of 0.84 (95% confidence interval = 0.76-0.93, = 0.001) and 0.84 (95% confidence interval = 0.73-0.97, = 0.021), respectively. Besides, expression quantitative trait loci analyses showed that these two survival-associated SNPs of and were significantly associated with their mRNA expression levels in both normal lung tissues and whole blood cells. Additional analyses suggested an oncogenic role for and a suppressor role for on the survival. Once further validated, genetic variants of and may be potential prognostic markers for NSCLC survival.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339263PMC
June 2020

Novel Variants of and in the Interferon Gamma Signaling Pathway Are Associated with Non-Small Cell Lung Cancer Survival.

Cancer Epidemiol Biomarkers Prev 2020 Aug 3;29(8):1679-1688. Epub 2020 Jun 3.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Background: IFNγ is a pleiotropic cytokine that plays critical immunomodulatory roles in intercellular communication in innate and adaptive immune responses. Despite recognition of IFNγ signaling effects on host defense against viral infection and its utility in immunotherapy and tumor progression, the roles of genetic variants of the IFNγ signaling pathway genes in survival of patients with cancer remain unknown.

Methods: We used a discovery genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial ( = 1,185) and a replication genotyping dataset from the Harvard Lung Cancer Susceptibility Study ( = 984) to evaluate associations between 14,553 genetic variants in 150 IFNγ pathway genes and survival of non-small cell lung cancer (NSCLC).

Results: The combined analysis identified two independent potentially functional SNPs, rs7242481G>A and rs1049493T>C, to be significantly associated with NSCLC survival, with a combined HR of 0.85 (95% confidence interval, 0.78-0.92; < 0.0001) and 0.87 (0.81-0.93; < 0.0001), respectively. Expression quantitative trait loci analyses showed that the survival-associated rs7242481A allele was significantly associated with increased mRNA expression levels of elongator acetyltransferase complex subunit 2 () in 373 lymphoblastoid cell lines and 369 whole-blood samples. The rs1049493C allele was significantly associated with decreased mRNA expression levels of in 383 normal lung tissues and 369 whole-blood samples.

Conclusions: Genetic variants of IFNγ signaling genes are potential prognostic markers for NSCLC survival, likely through modulating the expression of key genes involved in host immune response.

Impact: Once validated, these variants could be useful predictors of NSCLC survival.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415606PMC
August 2020

Rejection in the setting of non-HLA antibody: New tools for navigating bench to bedside.

Am J Transplant 2020 10 25;20(10):2639-2641. Epub 2020 May 25.

Department of Pathology, Duke University, Durham, North Carolina, USA.

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http://dx.doi.org/10.1111/ajt.15975DOI Listing
October 2020

Genotypes and Haplotypes in the Cholesterol-Related Pathway Genes Predict Non-Small Cell Lung Cancer Survival.

Cancer Epidemiol Biomarkers Prev 2020 06 1;29(6):1204-1213. Epub 2020 Apr 1.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Background: Several oncogenic signals are involved in the synthesis, metabolism, transportation, and modulation of cholesterol. However, the roles of genetic variants of the cholesterol pathway genes in cancer survival remain unclear.

Methods: We investigated associations between 26,781 common SNPs in 209 genes of the cholesterol pathway and non-small cell lung cancer (NSCLC) survival by utilizing genotyping data from two published genome-wide association studies. We used multivariate Cox proportional hazards regression and expression quantitative trait loci analyses to identify survival-associated SNPs and their correlations with the corresponding mRNA expression, respectively. We also used the Kaplan-Meier survival analysis and bioinformatics functional prediction to further evaluate the identified independent SNPs.

Results: We found five independent SNPs ( rs1801701C>T; rs35859010 C>T, rs1833970 T>A, rs254315 T>C, and rs425904 T>C) to be significantly associated with NSCLC survival in both discovery and replication datasets. When the unfavorable genotype ( rs1801701CC) and haplotypes ( rs35859010-rs1833970-rs254315-rs425904 C-A-T-C and T-T-T-T) were combined into a genetic score as the number of unfavorable genotypes/haplotypes (NUGH) in the multivariate analysis, an increased NUGH was associated with worse survival ( < 0.0001). In addition, both rs1801701T
Conclusions: Genetic variants of and in the cholesterol pathway were associated with NSCLC survival, possibly by affecting their gene expression.

Impact: Genetic variants of and in the cholesterol pathway may provide new scientific insights into NSCLC prognosis.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269811PMC
June 2020

Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer.

Int J Cancer 2020 09 9;147(6):1559-1570. Epub 2020 Mar 9.

Duke Cancer Institute, Duke University Medical Center, Durham, NC.

The ketone metabolism pathway is a principle procedure in physiological homeostasis and induces cancer cells to switch between glycolysis and oxidative phosphorylation for energy production. We conducted a two-phase analysis for associations between genetic variants in the ketone metabolism pathway genes and survival of nonsmall cell lung cancer (NSCLC) by analyzing genotyping data from two published genome-wide association studies (GWASs). In the discovery, we used a genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial in the multivariable Cox proportional hazards regression analysis. We used Bayesian false discovery probability (≤0.80) for multiple testing correction to evaluate associations between 25,819 (2,176 genotyped and 23,643 imputed) single-nucleotide polymorphisms (SNPs) in 162 genes and survival of 1,185 NSCLC patients. Subsequently, we validated the identified significant SNPs with an additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility GWAS study. Finally, we found that three independent and potentially functional SNPs in three different genes (i.e., PLIN2 rs7867814 G>A, SULT2A1 rs2547235 C>T and UGT1A9 rs2011404 C>T) were independently associated with risk of death from NSCLC, with a combined hazards ratio of 1.22 [95% confidence interval = 1.09-1.36 and p = 0.0003], 0.82 (0.74-0.91 and p = 0.0002) and 1.21 (1.10-1.33 and p = 0.0001), respectively. Additional expression quantitative trait loci analysis found that the survival-associated PLIN2 rs7867814 GA + AA genotypes, but not the genotypes of other two SNPs, were significantly associated with increased mRNA expression levels (p = 0.005). These results indicated that PLIN2 variants may be potential predictors of NSCLC survival through regulating the PLIN2 expression.
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http://dx.doi.org/10.1002/ijc.32932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078192PMC
September 2020

Novel genetic variants in HDAC2 and PPARGC1A of the CREB-binding protein pathway predict survival of non-small-cell lung cancer.

Mol Carcinog 2020 01 12;59(1):104-115. Epub 2019 Nov 12.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

The CREB-binding protein (CBP) pathway plays an important role in transcription and activity of acetyltransferase that acetylates lysine residues of histones and nonhistone proteins. In the present study, we hypothesized that genetic variants in the CBP pathway genes played a role in survival of non-small-cell lung cancer (NSCLC). We tested this hypothesis using the genotyping data from the genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In the single-locus analysis, we evaluated associations between 13 176 (1107 genotyped and 12 069 imputed) single-nucleotide polymorphisms (SNPs) in 72 genes and survival of 1185 patients with NSCLC. The identified 106 significant SNPs in the discovery were further validated in additional genotyping data from another GWAS dataset of 984 patients with NSCLC in the Harvard Lung Cancer Susceptibility Study. The combined results of two datasets showed that two independent, potentially functional SNPs (i.e., HDAC2 rs13213007G>A and PPARGC1A rs60571065T>A) were significantly associated with NSCLC overall survival, with a combined hazards ratio (HR) of 1.26 (95% confidence interval (CI), 1.09-1.45; P = .002) and 1.23 (1.04-1.47; P = .017), respectively. Furthermore, we performed an expression quantitative trait loci analysis and found that the survival-associated HDAC2 rs13213007A allele (GA+AA), but not PPARGC1A rs60571065A allele (TA+AA), was significantly associated with increased messenger RNA expression levels of HDAC2 in 373 lymphoblastoid cell lines. These results indicate that the HDAC2 rs13213007A allele is a potential predictor of NSCLC survival, likely by altering the HDAC2 expression.
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http://dx.doi.org/10.1002/mc.23132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481022PMC
January 2020

Novel genetic variants in KIF16B and NEDD4L in the endosome-related genes are associated with nonsmall cell lung cancer survival.

Int J Cancer 2020 07 19;147(2):392-403. Epub 2019 Dec 19.

Duke Cancer Institute, Duke University Medical Center, Durham, NC.

The endosome is a membrane-bound organ inside most eukaryotic cells, playing an important role in adaptive immunity by delivering endocytosed antigens to both MHC class I and II pathways. Here, by analyzing genotyping data from two published genome-wide association studies (GWASs), we evaluated associations between genetic variants in the endosome-related gene-set and survival of patients with nonsmall cell lung cancer (NSCLC). The discovery included 44,112 (3,478 genotyped and 40,634 imputed) single-nucleotide polymorphisms (SNPs) in 220 genes in a singlelocus analysis for their associations with survival of 1,185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. After validation of the 821 survival-associated significant SNPs in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study, 14 SNPs remained significant. The final multivariate stepwise Cox proportional hazards regression modeling of the PLCO dataset identified three potentially functional and independent SNPs (i.e., KIF16B rs1555195 C>T, NEDD4L rs11660748 A>G and rs73440898 A>G) with an adjusted hazards ratio (HR) of 0.86 (95% confidence interval [CI] = 0.79-0.94, p = 0.0007), 1.31 (1.16-1.47, p = 6.0 × 10 ) and 1.27 (1.12-1.44, p = 0.0001) for overall survival (OS), respectively. Combined analysis of the adverse genotypes of these three SNPs revealed a trend in the genotype-survival association (p < 0.0001 for OS and p < 0.0001 for disease-specific survival). Furthermore, the survival-associated KIF16B rs1555195T allele was significantly associated with decreased mRNA expression levels of KIF16B in both lung tissues and blood cells. Therefore, genetic variants of the endosome-related genes may be biomarker for NSCLC survival, possibly through modulating the expression of corresponding genes.
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http://dx.doi.org/10.1002/ijc.32739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096203PMC
July 2020

Molecular Analysis of a Patient With Neurofibromatosis 2 (NF2) and Peritoneal Malignant Mesothelioma.

Am J Surg Pathol 2020 02;44(2):288-292

Department of Pathology, Duke University Medical Center, Durham, NC.

Neurofibromatosis type 2 (NF2), an inherited disorder associated with multiple inherited schwannomas, meningiomas and ependymomas is caused by an autosomal dominant, likely loss of function germline mutation of the NF2 gene. Interestingly, biallelic NF2 gene inactivation is one of the most common mutations associated with the development of malignant mesothelioma (MM), a highly fatal malignancy that arises in the pleura and less frequently in the pericardium, peritoneum, and tunica vaginalis. It has been proposed that NF2 patients could potentially be at increased risk of developing MM. However, patients with inherited NF2 rarely develop MM. To date, only 2 cases describing patients diagnosed with both have been reported in the literature. Here, we describe the third case and for the first time, also provide molecular evidence that a "second hit" involving a somatic mutation is likely required to trigger the development of MM in this rare cohort. In our patient diagnosed with NF2 at age 25 who developed an aggressive peritoneal MM 15 years later, we identified a germline NF2 mutation and somatic mutations including BAP1. Of clinical relevance, our case supports a germline NF2 mutation may not necessarily be more susceptible to develop mesothelioma without a "second hit" mutation.
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http://dx.doi.org/10.1097/PAS.0000000000001359DOI Listing
February 2020

CD68/CD31 immunohistochemistry double stain demonstrates increased accuracy in diagnosing pathologic antibody-mediated rejection in cardiac transplant patients.

Am J Transplant 2019 11 9;19(11):3149-3154. Epub 2019 Sep 9.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.

Pathologic antibody-mediated rejection (pAMR) occurs in 10% of cardiac transplant patients and is associated with increased mortality. The endomyocardial biopsy remains the primary diagnostic tool to detect and define pAMR. However, certain challenges arise for the pathologist. Accurate identification of >10% of intravascular macrophages along with endothelial swelling, which remains a critical component of diagnosing pAMR, is one such challenge. We used double labeling with an endothelial and histiocytic marker to improve diagnostic accuracy. Twenty-two cardiac transplant endomyocardial biopsies were screened using a CD68/CD31 immunohistochemical (IHC) double stain. To determine whether pAMR diagnosis would change using the double stain, intravascular macrophage staining was compared to using CD68 alone. Twenty-two cardiac pAMR cases from patients were included. Fifty-nine percent of cases previously called >10% intravascular macrophage positive by CD68 alone were called <10% positive using the CD68/CD31 double stain. Not using the double stain was associated with a significant overcall. In C4d-negative cases, using the CD68/CD31 double stain downgraded the diagnosis of pAMR2 to pAMR1 in 32% of cases. It was concluded that more than one third of patients were overdiagnosed with pAMR using CD68 by IHC alone. We demonstrate the value of using a CD68/CD31 double stain to increase accuracy.
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http://dx.doi.org/10.1111/ajt.15540DOI Listing
November 2019

Pulmonary Granular Cell Tumors: A Study of 4 Cases Including a Malignant Phenotype.

Am J Surg Pathol 2019 10;43(10):1397-1402

Department of Pathology, Duke University Medical Center, Durham, NC.

Granular cell tumors are lesions of Schwannian phenotype that most frequently arise in the skin, breast, and tongue. Pulmonary granular cell tumors (pGCTs) are exceedingly rare and only a handful of cases worldwide have been reported as malignant. We report here a series of 4 pGCTs, including an extremely rare case of a malignant pGCT which underwent next-generation sequencing to identify a novel pathogenic mutation. We are the first to report any prognostic data and response to treatment. Consistent with granular cell tumors of other primary sites, the majority of pGCTs (75%) were deemed histologically and biological benign without metastasis or recurrence after resection (mean follow-up, 750 d). pGCTs occurred predominantly in women (75%) with a mean age of 57 years (range, 49 to 66 y) and variable smoking history. Notably, 2 women also developed an associated lung carcinoma (adenocarcinoma and small cell carcinoma). We also report here an exceedingly rare case of a 51-year-old nonsmoker woman diagnosed with a malignant pGCT. She presented with a 6.4×6.1×4.4 cm infrahilar left lower lobe mass with extrinsic compression and obstruction of the left mainstem on enhanced computed tomography. Pathology of the resection specimen confirmed a pGCT composed of sheets of tumor cells with pleural, pericardial, and diaphragmatic metastases. Molecular analysis by next-generation sequencing failed to yield any driver mutations common to primary lung adenocarcinomas. Only 2 previous malignant pGCTs have been reported; our case revealed a novel pathologic ATM mutation.
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http://dx.doi.org/10.1097/PAS.0000000000001303DOI Listing
October 2019

Thrombus on the inflow cannula of the HeartWare HVAD: an update.

Cardiovasc Pathol 2019 Jan - Feb;38:14-20. Epub 2018 Sep 15.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115. Electronic address:

Background: The HeartWare HVAD (Medtronic, Minneapolis, MN) is a continuous-flow left ventricular assist device (LVAD) approved by the FDA in 2012 as a bridge to transplant in patients with end-stage left ventricular heart failure. The current inflow cannula has a smooth outer surface near the inflow edge and a sintered collar of titanium microspheres near the pump. A previous case series of HVAD patients bridged to transplant revealed thrombus on the outer surface of the inflow cannula in 8 of 8 patients, predominantly at the smooth-sintered interface, that was associated with a clinical stroke rate of 12.5%.

Design: Cases of HVAD devices removed at the time of heart transplant were identified in the surgical pathology database. The gross and microscopic findings were reviewed along with clinical data.

Results: A total of 22 patients with 24 HVAD implants diagnosed with dilated cardiomyopathy (13 patients), ischemic heart disease (4 patients), lymphocytic myocarditis (2 patients), hypertrophic cardiomyopathy (2 patients), and congenital valvular disease (1 patient) were included. Two patients received two HVADs to provide biventricular support. All patients received post-implantation anti-coagulation with an INR goal of 2 to 3. Gross pathologic examination revealed thrombi on the outer aspect of the HVAD inflow cannula in 23 of 24 devices (96%). The inflow cannula of the one device that did not develop thrombus was positioned such that the smooth-sintered interface was buried in the ventricular myocardium and not in contact with blood in the ventricular chamber. Complications during the period of device support included 9 thromboembolic events (41%) including 6 ischemic strokes (27%), 2 intracoronary thromboembolic events and 1 splenic infarct. Patients suffered strokes 4 to 174 days (mean 82) after HVAD placement and had thrombus on the inflow cannula ranging in size from 0.1-2.5 cm (axial), 0.4-4.5 cm (circumferential) and 0.1-0.5 cm (thickness). Histologic evaluation revealed bland, partially organized thrombi without evidence of infection. Other complications included driveline infections (9%), non-driveline related bacteremia (9%) and hemorrhage (5%).

Conclusions: We report here an extension of our original study to a total of 22 patients with 24 HVAD implants who were all successfully bridged to transplant. We validate the very high prevalence of thrombus around the HVAD inflow cannula, associated with a clinical thromboembolic event in over a third of the patients, the majority of which were strokes. The nidus for thrombus formation appears to be the smooth-sintered interface of the HVAD inflow cannula.
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http://dx.doi.org/10.1016/j.carpath.2018.09.002DOI Listing
March 2019

Unique Intradural Inflammatory Mass Containing Precipitated Morphine: Confirmatory Analysis by LESA-MS and MALDI-MS.

Pain Pract 2018 09 30;18(7):889-894. Epub 2018 Mar 30.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.

Opioids are often used for analgesia via continuous intrathecal delivery by implantable devices. A higher concentration and daily dose of opioid have been postulated as risk factors for intrathecal granuloma formation. We present a 42-year-old female patient with chronic abdominal pain from refractory pancreatitis, with an intrathecal drug delivery device implanted 21 years prior, delivering continuous intrathecal morphine. After many years without concerning physical signs or complaints, with gradual increases in daily morphine dose, she presented with rapidly progressive neurologic deficits, including lower extremity, bladder, and bowel symptoms. These symptoms were determined to be secondary to mass effect and local inflammation related to an intrathecal catheter tip granuloma, detected on magnetic resonance imaging of the spine. The mass was urgently resected. On histopathologic examination, this granuloma was found to be unique, in that in addition to the expected inflammatory components, it appeared to contain precipitated nonpolarizable crystals. These were identified as precipitated morphine using liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) and matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MALDI-FTICR-MSI). In addition to the unique finding of precipitated morphine crystals, the long-term follow-up of both morphine concentration and daily dose increases provides insight into the formation of intrathecal granulomas.
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http://dx.doi.org/10.1111/papr.12688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109606PMC
September 2018

Natural history of cranial fibrous dysplasia revealed during long-term follow-up: Case report and literature review.

Surg Neurol Int 2017 6;8:209. Epub 2017 Sep 6.

Department of Neurological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: Fibrous dysplasia (FD) is a rare developmental disease characterized by the replacement of bone marrow with proliferating fibro-osseous tissue. There exist three forms of FD-monostotic, polyostotic, and that associated with McCune-Albright syndrome. The disease can present in different locations and with a variety of symptoms. One of the more common locations of FD occurrence is the craniofacial region. Treatment of asymptomatic FD often involves conservative management with serial imaging. Medical management with bisphosphonates is an option, though long-term efficacy data are lacking. Surgical resection is usually reserved for very large or symptomatic lesions.

Case Description: We discuss the most unusual case of a 52-year-old male found to have a left pterional mass while being worked up for sinus headaches. The patient elected to follow this lesion conservatively, and imaging several years later showed obvious growth which accelerated in the last 4 years during an 18-year observational period. He ultimately underwent successful resection of an extradural and intradural FD.

Conclusions: The significant growth potential of these lesions was revealed in this patient, in whom conservative management had been adopted. Despite optimal surgical resection and outcome in this case, the importance of surveillance imaging and perhaps earlier intervention cannot be underestimated when managing cranial FD.
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http://dx.doi.org/10.4103/sni.sni_7_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609397PMC
September 2017

Winning the battle, but losing the war: mechanisms and morphology of cancer-therapy-associated cardiovascular toxicity.

Cardiovasc Pathol 2017 Sep - Oct;30:55-63. Epub 2017 Jun 30.

Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Electronic address:

In the United States, the lifetime risk of a cancer diagnosis is nearly 40%; in 2016, that represents almost 1.6 million new patients, and despite advances in early diagnosis and treatment, roughly 35% will ultimately die of their malignancy. Fortunately, the number of patients living with a cancer diagnosis also continues to expand, anticipated to be more than 19 million in less than a decade. In calculating the relative risks and benefits of therapy, it is therefore important to consider the morbidity and mortality associated with antitumor therapy itself. Significantly, excluding demise due to the malignancy itself, treatment-induced adverse cardiovascular events are the leading cause of death in cancer patients. Chemotherapy, targeted therapies, immune checkpoint inhibition, and radiation therapy can all adversely impact cardiac function, and their effects can be synergistic. Consequently, it is important that possible side effects of therapy be recognized and effectively controlled. This review highlights the mechanisms and histopathologic findings associated with common forms of potentially cardiotoxic cancer therapy including anthracyclines, tyrosine kinase inhibitors, and most recently immune checkpoint (PD-1) inhibitors. Although for many cases the histologic findings are nonspecific, in the appropriate clinical context, therapeutic cardiotoxicity can be inferred and the treatment approach refined appropriately.
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http://dx.doi.org/10.1016/j.carpath.2017.06.009DOI Listing
May 2018

Use of Multimodality Imaging in Diagnosing Invasive Fungal Diseases of the Heart.

Circ Cardiovasc Imaging 2017 06;10(6)

From the Department of Medicine (E.M.D.), Cardiovascular Imaging Program, Departments of Medicine and Radiology (S.C., S.P., A.A., M.F.D., R.B.), Department of Pathology (C.G., R.N.M.), and Division of Infectious Disease, Department of Medicine (R.M.M.), Brigham and Women's Hospital, Boston, MA.

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http://dx.doi.org/10.1161/CIRCIMAGING.117.006550DOI Listing
June 2017

Giant cell aortitis mimicking intramural hematoma.

J Cardiovasc Comput Tomogr 2017 Jul - Aug;11(4):327-328. Epub 2017 Feb 4.

Cardiovascular Imaging Program, Department of Radiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States.

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http://dx.doi.org/10.1016/j.jcct.2017.02.001DOI Listing
November 2018

The role of EVI1 in myeloid malignancies.

Blood Cells Mol Dis 2014 Jun-Aug;53(1-2):67-76. Epub 2014 Feb 1.

Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA. Electronic address:

The EVI1 oncogene at human chr 3q26 is rearranged and/or overexpressed in a subset of acute myeloid leukemias and myelodysplasias. The EVI1 protein is a 135 kDa transcriptional regulator with DNA-binding zinc finger domains. Here we provide a critical review of the current state of research into the molecular mechanisms by which this gene plays a role in myeloid malignancies. The major pertinent cellular effects are blocking myeloid differentiation and preventing cellular apoptosis, and several potential mechanisms for these phenomena have been identified. Evidence supports a role for EVI1 in inducing cellular quiescence, and this may contribute to the resistance to chemotherapy seen in patients with neoplasms that overexpress EVI1. Another isoform, MDS1-EVI1 (or PRDM3), encoded by the same locus as EVI1, harbors an N-terminal histone methyltransferase(HMT) domain; experimental findings indicate that this protein and its HMT activity are critical for the progression of a subset of AMLs, and this provides a potential target for therapeutic intervention.
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http://dx.doi.org/10.1016/j.bcmd.2014.01.002DOI Listing
January 2015

Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia.

Blood 2013 Oct 10;122(16):2888-92. Epub 2013 Sep 10.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY; and.

A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs) including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR) domain with histone methyltransferase activity in the ME isoform. Using an ME-deficient mouse, we show that ME is required for MLL-AF9-induced transformation both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective, indicating that the ME requirement is specific to MLL fusion leukemia. Further, we show that the PR domain is essential for MFP-induced transformation. These studies clearly indicate an essential role of PR-domain protein ME in MFP leukemia, suggesting that ME may be a novel target for therapeutic intervention for this group of leukemias.
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http://dx.doi.org/10.1182/blood-2012-08-453662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799001PMC
October 2013

Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

PLoS One 2013 27;8(6):e67134. Epub 2013 Jun 27.

Department of Pathology and Lab Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.

The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694976PMC
October 2017

Recruiting strategies for potential 0+5 vascular residency applicants.

Ann Vasc Surg 2012 Jan 20;26(1):1-9. Epub 2011 Jul 20.

Department of Surgery, Division of Vascular Surgery, The University of Rochester Medical Center, Rochester, NY 14642, USA.

Background: The 0+5 integrated vascular residency training pathway was established in 2006 to allow for trainee-focused training culminating in vascular surgery certification only. An early concern was whether enough medical students could be recruited directly into a vascular internship without the exposure that a general surgery residency provides. We hypothesized that programs that send a large percentage of their general surgical graduates to vascular fellowships have models that can be adapted to medical student recruitment.

Methods: Opinions and practices were sought from program directors through survey and from trainees taking the Vascular Surgery In-Training Examination.

Results: Eight programs were identified that sent 20% or more of their residents to vascular fellowships over the past 5 years (projecting a mean of 1.6 residents entering vascular fellowships in 2011). Almost all such programs have a formal mentoring system in place that match mentors to residents by interest, and almost all send residents to academic meetings before their senior year. Seventy-five percent of such programs have formal vascular lecture exposure to the first and second year medical student classes, offer clinical shadowing experiences, and have time on the vascular service during the MS3 clerkship; 83% offer a third- or fourth-year elective in vascular surgery. Vascular Surgery In-Training Examination responses were collected from 156 fellows and 13 "0+5" residents. Although fellows had initially been attracted to vascular surgery by the technical aspects of the field learned during residency (43%), the most important factor initially attracting medical students was an interested mentor (46%). However, the most important factor for both residents and students in making a final decision was the technical aspects of the field (66% and 63%, respectively).

Conclusions: Although residents are automatically exposed to the field during residency, students can only be exposed to vascular surgery if a conscious effort is made by interested educators. Programs that send a high proportion of students and residents into vascular surgery tend to have planned exposure at the MS1 and MS2 levels, formal clinical rotations in place at the MS3 and MS4 levels, and pay personal attention to those who display interest. A guide is presented to help specifically plan these steps. Successful recruiting of students into a 0+5 integrated training program requires specific planning and action.
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http://dx.doi.org/10.1016/j.avsg.2011.04.003DOI Listing
January 2012

Costoclavicular venous decompression in patients with threatened arteriovenous hemodialysis access.

Ann Vasc Surg 2011 Jul 21;25(5):640-5. Epub 2011 Apr 21.

Division of Vascular Surgery, University of Rochester Medical Center, Rochester, NY, USA.

Background: Autologous arteriovenous fistulas are frequently threatened by central venous obstruction. Although this is frequently ascribed to indwelling catheters and neointimal venous remodeling, we believe that extrinsic compression of the subclavian vein as it passes through the costoclavicular junction (CCJ) may play a significant role in a subset of dialysis patients.

Methods: We reviewed our experience with CCJ decompression for arteriovenous fistula dysfunction at our institution. Decompression followed principles for venous thoracic outlet syndrome: bony decompression with thorough venolysis, followed by central venography through the fistula and endoluminal treatment, if necessary. Patients underwent transaxillary first rib resection, or claviculectomy in the supine position in cases when reconstruction was anticipated. In all cases, the minimum exposure included 360° mobilization of the subclavian vein with resection of surrounding cicatrix to the jugular/innominate junction.

Results: A total of 10 patients requiring decompression between November 2008 and February 2010 were included. All had severe arm swelling, four had dialysis dysfunction (postcannulation bleeding or maturation failure), two had severe arm pain, and one had a pseudoaneurysm. All patients had subclavian vein stenosis at the CCJ by venography or intravascular ultrasound. The majority of patients had balloon dilation (mean: 2.3 attempts) without success. Six patients underwent transaxillary first rib resection and four had medial claviculectomy. No patients required surgical venous reconstruction. In all, 80% of fistulas remained functionally patent, and all but one patient (who underwent ligation) had complete relief of upper arm edema. Median hospital length of stay was 2 days and mean follow-up was 7 months (range, 1-13). There was no mortality or significant morbidity. Five patients later required central venoplasty (four subclavian, mean: 1.8 attempts and one innominate) and three had stents placed (two subclavian, one innominate).

Conclusion: A significant number of patients with threatened AV access owing to central venous obstruction have lesions attributable to compression at the CCJ. Surgical decompression by means of first rib or clavicular resection and thorough external venoloysis allowed symptom-free functional salvage in 80% of these patients, all of whom would have lost their access otherwise. Because surgical reconstruction is seldom needed, the transaxillary approach may be preferable to claviculectomy. This lesion should be specifically looked for, and principles of venous thoracic outlet syndrome treatment seem to apply and be effective.
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http://dx.doi.org/10.1016/j.avsg.2010.12.020DOI Listing
July 2011

Midabdominal aortic coarctation presenting with severe pre-eclampsia.

J Vasc Surg 2011 Aug 11;54(2):511-4. Epub 2011 Mar 11.

Division of Vascular Surgery, University of Rochester Medical Center, Rochester, NY, USA.

This is a case report of a 23-year-old pregnant woman with uncontrolled hypertension, resulting in delivery of her baby at 28 weeks. Postpartum, she further developed claudication and postprandial abdominal discomfort and was diagnosed with coarctation of the midabdominal aorta. She underwent thoracoabdominal aortic repair from the descending thoracic to infrarenal aorta. A bifurcated graft was used to complete the aorto-common hepatic artery and aorto-superior mesenteric artery bypasses. A third graft limb was sewn to revascularize the left renal artery. At 1-year follow up, all symptoms had resolved. This is an interesting coarctation patient treated successfully with thoracoabdominal reconstruction.
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http://dx.doi.org/10.1016/j.jvs.2010.12.021DOI Listing
August 2011

Long-term results of endoscopic versus open saphenous vein harvest for lower extremity bypass.

Ann Vasc Surg 2011 Jan;25(1):101-7

Department of Surgery, University of Rochester Medical Center, NY 14642, USA.

Background: Endoscopic saphenous vein harvest (EVH) has been shown to lower wound infection rates and cost compared with conventional harvest, although long-term patency data are lacking. A small series of studies has recently suggested that patency is inferior to conventionally harvested vein technique, and we thus sought to explore this question by reviewing our cumulative experience with this technique.

Methods: The short- and long-term outcomes of all lower extremity bypasses (LEBPs) using saphenous vein at one institution over a period of 8.5 years were retrospectively reviewed.

Results: A total of 363 patients averaging 67 ± 24 to 100 years of age had undergone LEBP and had charts available for review. Of these 363 patients, 170 underwent EVH (90% using a noninsufflation technique) and 193 conventional (by means of continuous or skip incisions); 48% of patients reported tissue loss and no differences in indication for surgery were noted between groups. Mean follow-up was 35.1 (range: <1-105) months. Primary patency rates were worse in the EVH group as compared with conventional at six (63.3% ± 4.0% vs. 77.3% ± 3.3%), 12 (50.4% ± 4.2% vs. 73.7% ± 3.6%), and 36 (42.2% ± 4.5% vs. 59.1% ± 4.9%) months (all p < 0.001), although these differences were largely limited to patients with limb-threat and diabetes. However, limb salvage and survival, were identical between groups. Contrary to previous experience, there were no differences in length of stay or wound complication rates.

Conclusions: The overall results of this study show an inferior long-term patency rate for endoscopically harvested saphenous vein after LEBP in our series as a whole, and do not confirm the short-term benefit previously shown in a selected cohort. These differences were, however, minimal or absent in patients with claudication or absence of diabetes, and EVH may continue to play a role in these cases.
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http://dx.doi.org/10.1016/j.avsg.2010.10.013DOI Listing
January 2011