Publications by authors named "Neda Hashemi Sadraei"

11 Publications

  • Page 1 of 1

Prolonged Response to Anti-PD-1 Antibody Therapy in Chemotherapy-Refractory Cholangiocarcinoma With High Tumor Mutational Burden.

J Natl Compr Canc Netw 2019 06;17(6):644-648

Indiana University School of Medicine, Indianapolis, Indiana.

Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease.
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http://dx.doi.org/10.6004/jnccn.2019.7304DOI Listing
June 2019

Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients.

Hum Pathol 2019 08 3;90:27-36. Epub 2019 May 3.

Indiana University, Department of Pathology and Laboratory Medicine, Indianapolis, IN 46202.

Accurate diagnosis of plasmacytoid urothelial carcinoma (PUC) is important given its poor prognosis and frequent presentation at high stage. We aim to assess the clinicopathological features, molecular aberrations, and follow-up data in a series of PUC cases from a single tertiary cancer center. Seventy-two urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation were identified. Immunohistochemical stains were performed on 48 cases. Among urinary bladder origin markers, GATA3 was most sensitive (96%). Breast carcinoma markers (estrogen receptor, mammaglobin) were usually negative, but progesterone receptor stained 1 case (4%). Neuroendocrine markers CD56 and TTF-1 were each positive in 1 case (4% and 4%, respectively). Gastrointestinal adenocarcinoma marker CDX2 was positive in 4 cases (15%), but nuclear β-catenin was negative in all cases. CD138 was positive in 83% and E-cadherin expression was lost in 57% of cases. Fluorescence in situ hybridization using the UroVysion Bladder Cancer Kit and FGFR3 mutational analysis using polymerase chain reaction were performed on 15 cases; deletion of chromosome 9p21 was common (60%), and FGFR3 mutations were detected in 60% of cases (5 cases had both deletion 9p21 and FGFR3 mutations). Cases were divided into 3 morphologic groups: classic (29%), desmoplastic (35%), and pleomorphic (36%). The 3 morphologic subtypes had distinct survival outcomes (P = .083), with median survival for all patients 18 being months versus 10 months for the desmoplastic group.
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http://dx.doi.org/10.1016/j.humpath.2019.04.012DOI Listing
August 2019

Clinical Characteristics of Patients Experiencing Pathologic Complete Response Following Neoadjuvant Therapy for Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma.

Am J Clin Oncol 2018 10;41(10):982-985

Departments of Medicine.

Objectives: The purpose of this study is to describe clinical characteristics and outcomes of patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who achieved pathologic complete response (pCR) following neoadjuvant therapy.

Materials And Methods: A single institution clinical database for patients with pancreatic ductal adenocarcinoma was queried. Between 2008 and 2014 patients were identified with BRPC and LAPC, who underwent surgical resection after receiving neoadjuvant treatment. Clinical and pathologic features of the patients who achieved pCR were acquired retrospectively.

Results: Six patients were identified to have pCR on pathology of the postoperative specimen. On the basis of pretreatment clinical staging, 2 patients were considered to have BRPC and 4 LAPC. Four patients received gemcitabine-based chemotherapy and 2 patients received FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin). Five of 6 patients received radiation therapy before operative resection. Operative procedures included distal pancreatectomy (n=3) and pancreatoduodenectomy (n=3). Pancreatic intraepithelial neoplasia 1 to 2 was present in 3 cases, and pancreatic intraepithelial neoplasia 3 in 1 case. During a median follow-up of 21.3 months, 2 patients died, with a median survival of 11.0 months (range, 10.4 to 11.6 mo). Four patients are alive and continue to follow-up with median survival of 28.7 months (range, 20.1 to 42.4 mo).

Conclusions: Multimodality neoadjuvant therapy may lead to complete pathologic response in a small number of patients with borderline resectable/locally advanced pancreatic adenocarcinoma. pCR to neoadjuvant therapy does not lead to cure in most cases, and the majority of patients appear to relapse locally or systemically.
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http://dx.doi.org/10.1097/COC.0000000000000409DOI Listing
October 2018

Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3?

Am J Surg Pathol 2017 Oct;41(10):1397-1402

Departments of *Pathology †Urology ¶¶Radiology, University of Alabama at Birmingham, Birmingham, AL Departments of ‡Pathology ∥Biostatistics ‡‡Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN §Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD ¶Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA #Department of Pathology, Keck School of Medicine of University of Southern California ∥∥Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles **Department of Pathology, Stanford Medicine, Stanford, CA ††Department of Pathology, Lenox Hill Hospital, New York, NY §§Department of Pathology, University of Michigan, Ann Arbor, MI ##Department of Pathology, University of Pennsylvania, Philadelphia, PA.

The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.
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http://dx.doi.org/10.1097/PAS.0000000000000917DOI Listing
October 2017

Targeting FGFR in Squamous Cell Carcinoma of the Lung.

Target Oncol 2017 12;12(6):741-755

Department of Medicine, Indiana University School of Medicine, 535 Barnhill Drive, RT 400, Indianapolis, IN, 46202, USA.

Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy. Several multi-targeted tyrosine kinase inhibitors include FGFR in their target spectrum and a number of these compounds have been approved for clinical use in different cancers. Novel agents selectively targeting FGFRs have been developed and are currently under investigation in clinical trials, showing promising results. This article reviews FGFR aberrations and the clinical data involving selective and multikinase FGFR inhibitors in squamous cell lung cancer.
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http://dx.doi.org/10.1007/s11523-017-0513-6DOI Listing
December 2017

The Significance of Lymphovascular Invasion of the Spermatic Cord in the Absence of Cord Soft Tissue Invasion.

Arch Pathol Lab Med 2017 Jun 31;141(6):824-829. Epub 2017 Mar 31.

From the Departments of Pathology (Drs McCleskey and Gordetsky), Urology (Drs Rais-Bahrami and Gordetsky), and Radiology (Dr Rais-Bahrami), University of Alabama, Birmingham; the Department of Pathology, University of Michigan, Ann Arbor (Dr Jorns); the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (Dr Lu); the Department of Pathology, Brown University, Providence, Rhode Island (Dr Matoso); the Department of Pathology, University of Pennsylvania, Philadelphia (Dr Schwartz); the Departments of Hematology/Oncology (Drs Albany and Hashemi-Sadraei) and Pathology (Drs Idrees and Ulbright), Indiana University School of Medicine, Indianapolis; and the Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland (Dr. Epstein).

Context: - Testicular germ cell tumors with lymphovascular invasion (LVI) are staged pT2, and those with spermatic cord involvement are staged pT3.

Objective: - To study the clinical significance of LVI within the spermatic cord without direct involvement of the cord soft tissues.

Design: - A retrospective, multi-institutional review was performed on testicular GCTs with spermatic cord LVI in the absence of cord soft tissue invasion.

Results: - Forty-four germ cell tumors had LVI in the spermatic cord without soft tissue invasion; 37 of 44 patients (84%) had nonseminomatous germ cell tumors (NSGCT), and 7 (16%) had pure seminomas. Patients with NSGCTs and spermatic cord LVI had worse clinical outcomes compared with patients with pure seminoma and spermatic cord LVI (P = .008). We then compared patients with NSGCTs and spermatic cord LVI (n = 37) to patients with NSGCTs and LVI limited to the testis (n = 32). A significantly greater percentage of patients with LVI in the spermatic cord presented with advanced clinical stage (76% versus 50%; P = .01). There was no statistically significant difference in disease recurrence/progression or death between patients with spermatic cord LVI and patients with LVI limited to the testis (P = .40; P = .50). There was no significant difference in the presence of embryonal dominant histology (P = .30) or rete testis invasion (P = .50) between the 2 groups. More hilar soft tissue invasion was seen in patients with LVI present in the spermatic cord (P = .004).

Conclusions: - In patients with NSGCTs, LVI in the spermatic cord, without soft tissue invasion, is associated with worse clinical stage at presentation compared with patients with LVI confined to the testis.
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http://dx.doi.org/10.5858/arpa.2016-0226-OADOI Listing
June 2017

Epstein-barr virus-related hemophagocytic lymphohistiocytosis: hematologic emergency in the critical care setting.

Case Rep Hematol 2015 10;2015:491567. Epub 2015 Feb 10.

Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potential life-threatening clinical syndrome that results from uncontrolled activation of the immune system. Secondary HLH, more commonly observed in adult patients, is seen in the context of underlying triggering conditions. Epstein-Barr virus (EBV) has been recognized as the leading infectious cause and is associated with a poor outcome. As clinical and laboratory features of HLH could overlap with septic shock syndrome in most patients, the diagnosis of HLH, especially in adults, is the most challenging aspect of the disease that results in delayed recognition and treatment of rapidly progressive multiorgan system failure. We report a case of Hemophagocytic lymphohistiocytosis in a patient who presented with signs of septic shock syndrome and we review the literature on the topic.
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http://dx.doi.org/10.1155/2015/491567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338404PMC
March 2015

Bilateral Acromioclavicular Septic Arthritis as an Initial Presentation of Streptococcus pneumoniae Endocarditis.

Case Rep Infect Dis 2014 1;2014:313056. Epub 2014 Jun 1.

Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.134, Houston, TX 77030, USA.

Infective endocarditis (IE) is infrequently associated with septic arthritis. Moreover, septic arthritis of the acromioclavicular (AC) joint is rarely reported in the literature. We report a case of Streptococcus pneumoniae IE in a patient who presented with bilateral AC joint septic arthritis and we review the literature on the topic.
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http://dx.doi.org/10.1155/2014/313056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058585PMC
July 2014

Lactic acidosis in gastric cancer.

J Gastrointest Cancer 2014 Dec;45 Suppl 1:192-4

Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.122, Houston, TX, 77030, USA,

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http://dx.doi.org/10.1007/s12029-014-9623-xDOI Listing
December 2014

Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges.

Onco Targets Ther 2013 15;6:371-89. Epub 2013 Apr 15.

Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH.

High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.
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http://dx.doi.org/10.2147/OTT.S38628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633547PMC
April 2013

Idiopathic pulmonary fibrosis in a referral center in Iran: are patients developing the disease at a younger age?

Arch Iran Med 2013 Mar;16(3):177-81

Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.

Unlabelled:  

Background: The incidence of idiopathic pulmonary fibrosis (IPF) appears to be increasing.  In the western literature, the average age of presentation is in the seventh decade of life while it has been reported to be earlier in the Middle East and India.  Given that a paucity of epidemiological data exists in Iran, we sought to describe the clinical pattern and course of the disease at a large Iranian referral center.

Methods: A retrospective review was conducted of 132 patients diagnosed with IPF at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD) in Tehran, Iran from 1988 through 2008. Data were collected from the medical records which consisted of demographics, clinical history, laboratory tests, pulmonary function tests (PFT), radiographic and pathology findings, treatment, and outcomes of the disease.  

Results: The mean age at diagnosis was 56.6 years (95% CI: 53.8 - 59.4) with no significant sex predilection. Common presenting symptoms included dyspnea and cough, which occurred for a mean period of 21 months prior to diagnosis. Common signs included end-inspiratory crackles and digital clubbing, which were found in 85.6% and 55.3% of the patients, respectively. Radiographically, reticular and reticulonodular opacities were seen in 47.3% and 20.9% of the patients, respectively on high resolution computed tomography (HRCT). In patients who underwent lung biopsy, diffuse interstitial fibrosis was seen in 91.1%. The mean follow-up time for all patients was 32.8 months (95% CI: 23.2 - 42.4, range: 1 - 257 months).  There were 16 patients who died during the study period. The mean age of death was 56.8 years (95% CI: 46.2 - 67.4), which is significantly lower than the life expectancy in Iran (P-value: 0.017). The mean survival time for patients who died was 1.1 years (95% CI: 0.5 - 1.7) after diagnosis.  The one- and three- year overall survival rates for all patients were 88% and 79%, respectively. 

Conclusion: The clinical characteristics of IPF in Iran are similar to those in the western literature.  However, Iranian patients appear to be developing the disease a decade earlier than western patients.
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http://dx.doi.org/013163/AIM.0011DOI Listing
March 2013