Analysis of long-term clinical and cost impact of etranacogene dezaparvovec for the treatment of hemophilia B population in the United States.

Introduction: Etranacogene dezaparvovec (EDZ), Hemgenix, is a gene therapy recently approved for people with hemophilia B (PwHB).

Objective: To estimate long-term clinical impact and cost of EDZ in the United States (US).

Methods: A decision-analytic model was developed to evaluate the long-term impact of introducing EDZ for PwHB over a 20-year time horizon.

Assessing health plan payer's budget impact of etranacogene dezaparvovec for the treatment of hemophilia B in the United States.

Background: Etranacogene dezaparvovec is a recently approved gene therapy for people with hemophilia B (PwHB). Current standard of care is prophylaxis with factor IX (FIX) to prevent bleeding. Etranacogene dezaparvovec increases blood FIX levels such that FIX prophylaxis could be eliminated.

Risk factors for postpolypectomy bleeding in patients receiving anticoagulation or antiplatelet medications.

Background And Aims: Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge and other antithrombotic therapy.

Methods: We performed a retrospective cohort and case control study at 2 tertiary-care medical centers from 2004 to 2012.

In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer.

Optical molecular imaging holds the potential to improve cancer diagnosis. Fluorescent nanoparticles such as quantum dots (QD) offer superior optical characteristics compared to organic dyes, but their in vivo application is limited by potential toxicity from systemic administration. Topical administration provides an attractive route for targeted nanoparticles with the possibility of minimizing exposure and reduced dose.

Patients With Nonpolypoid (Flat and Depressed) Colorectal Neoplasms at Increased Risk for Advanced Neoplasias, Compared With Patients With Polypoid Neoplasms.

Background & Aims: Nonpolypoid colorectal neoplasms (NP-CRNs) are more likely to contain high-grade dysplasia or early-stage cancer than polypoid neoplasms. We aimed to determine the long-term outcomes of patients with at least 1 NP-CRN.

Methods: We performed a longitudinal cohort study of 4454 patients at a Veterans' Affairs hospital who underwent colonoscopy from 2000 through 2005; 341 were found to have 1 or more NP-CRNs and were matched (3:1) with patients found to have 1 or more polypoid neoplasms (controls, n = 1025).

Intraoperative Optical Biopsy during Robotic Assisted Radical Prostatectomy Using Confocal Endomicroscopy.

Purpose: Intraoperative optical biopsy technologies may aid in the identification of important anatomical landmarks and improve surgical outcomes of robotic assisted radical prostatectomy. We evaluate the feasibility of confocal laser endomicroscopy during robotic assisted radical prostatectomy.

Materials And Methods: A total of 21 patients with biopsy proven prostate cancer scheduled for robotic assisted radical prostatectomy were recruited.

Does Better Specimen Orientation and a Simplified Grading System Promote More Reliable Histologic Interpretation of Serrated Colon Polyps in the Community Practice Setting? Results of a Nationwide Study.

Introduction: Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable.

Large Sessile Serrated Polyps Can Be Safely and Effectively Removed by Endoscopic Mucosal Resection.

Background & Aims: As many as 50% of large sessile serrated adenomas/polyps (SSPs) are removed incompletely, which is significant because SSPs have been implicated in the development of interval cancers. It is unclear if endoscopic mucosal resection (EMR) is an optimal method for removal of SSPs. We assessed the efficacy and safety of removal of SSPs 10 mm and larger using a standardized inject-and-cut EMR technique.

A Pilot Study of In Vivo Confocal Laser Endomicroscopy of Upper Tract Urothelial Carcinoma.

Purpose: Tissue diagnosis of upper tract urothelial carcinoma (UTUC) is limited by variance in tumor sampling by standard ureteroscopic biopsy. Optical imaging technologies can potentially improve UTUC diagnosis, surveillance, and endoscopic treatment. We previously demonstrated in vivo optical biopsy of urothelial carcinoma of the bladder using confocal laser endomicroscopy (CLE).

Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid.

Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura.

Real-time optical diagnosis for diminutive colorectal polyps using narrow-band imaging: the VALID randomised clinical trial.

Background: Diminutive (≤ 5 mm) colorectal polyps are common, and overwhelmingly benign. Routinely, after polypectomy, they are examined pathologically to determine the surveillance intervals. Advances in equipment and techniques, such as narrow-band imaging (NBI) colonoscopy, now permit reliable real-time optical diagnosis.

Endoscopic molecular imaging of human bladder cancer using a CD47 antibody.

A combination of optical imaging technologies with cancer-specific molecular imaging agents is a potentially powerful strategy to improve cancer detection and enable image-guided surgery. Bladder cancer is primarily managed endoscopically by white light cystoscopy with suboptimal diagnostic accuracy. Emerging optical imaging technologies hold great potential for improved diagnostic accuracy but lack imaging agents for molecular specificity.

Endoscopists can sustain high performance for the optical diagnosis of colorectal polyps following standardized and continued training.

Background And Study Aims: The learning curve for optical diagnosis of colorectal polyps with the narrow-band imaging (NBI) is unknown. To forego histological analysis of diminutive polyps diagnosed optically with high confidence, guidelines recommend ≥ 90 % negative predictive value (NPV) and concordance of ≥ 90 % for surveillance intervals predicted optically and histologically. We aimed to study the learning of optical diagnosis for colorectal polyps.

A simple tissue-handling technique performed in the endoscopy suite improves histologic section quality and diagnostic accuracy for serrated polyps.

Background And Study Aims: Surveillance intervals after colonoscopic resection of serrated polyps are partially predicated on the histology of the polyp(s) removed during the index exam. Histologic discrimination between sessile serrated adenomas/polyps (SSA/P) and hyperplastic polyps is challenging. We devised and tested a simple tool--an envelope--that gastroenterologists can integrate into routine colonoscopy practice to address this problem.

Pathologic predictive factors for lymph node metastasis in submucosal invasive (T1) colorectal cancer: a systematic review and meta-analysis.

Background: Colorectal adenocarcinoma with depth of invasion ≤1,000 μm from the muscularis mucosa and favorable histology is now considered for local resection. We aimed to examine the strength of evidence for this emerging practice.

Methods: We searched Medline, Scopus, and Cochrane (1950-2011), then performed a meta-analysis on the risk of lymph node metastasis in nonpedunculated (sessile and nonpolypoid) T1 colorectal cancers.

Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.).

Interobserver agreement of confocal laser endomicroscopy for bladder cancer.

Background And Purpose: Emerging optical imaging technologies such as confocal laser endomicroscopy (CLE) hold promise in improving bladder cancer diagnosis. The purpose of this study was to determine the interobserver agreement of image interpretation using CLE for bladder cancer.

Methods: Experienced CLE urologists (n=2), novice CLE urologists (n=6), pathologists (n=4), and nonclinical researchers (n=5) were recruited to participate in a 2-hour computer-based training consisting of a teaching and validation set of intraoperative white light cystoscopy (WLC) and CLE video sequences from patients undergoing transurethral resection of bladder tumor.

Histologic and molecular analyses of colonic perineurial-like proliferations in serrated polyps: perineurial-like stromal proliferations are seen in sessile serrated adenomas.

Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts.

Microfluidics-based diagnostics of infectious diseases in the developing world.

One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples.

Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases.

The diagnosis of metastatic clear cell renal cell carcinoma (CC-RCC) can be difficult because of its morphologic heterogeneity and the increasing use of small image-guided biopsies that yield scant diagnostic material. This is further complicated by the degree of morphologic and immunophenotypic overlap with nonrenal neoplasms and tissues, such as adrenal cortex. In this study, a detailed immunoprofile of 63 adrenal cortical lesions, which included 54 cortical neoplasms, was compared with 185 metastatic CC-RCCs using traditional [anticalretinin, CD10, antichromogranin, antiepithelial membrane antigen, anti-inhibin, antimelanA, anticytokeratins (AE1/AE3 and AE1/CAM5.

Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases.

Brachyury is recognized as a specific marker for notochord-derived tissues and neoplasms, and has become a defining immunohistochemical feature of chordoma. The main differential diagnostic consideration for chordoma is chondrosarcoma, which is known to lack brachyury expression. However, within the spectrum of genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell carcinoma may also be close morphological mimics of chordoma, particularly given the increasing prevalence of small tissue samples from image-guided biopsies.

Is lymphadenectomy indicated in patients with T1 moderately differentiated penile cancer?

Objective: In patients with penile squamous cell carcinomas (SCCs), lymphadenectomy can be curative and should be considered in cases deemed high risk for metastatic spread to regional lymph nodes. Management of patients without palpable lymphadenopathy remains controversial. Current guidelines for T1 penile SCCs based on previous studies have suggested that moderately differentiated tumors are at low risk for metastatic disease; however given our experience with such patients we sought to examine whether such tumors were truly observable or should be treated more aggressively.