Development of Patient-Derived Gastric Cancer Organoids from Endoscopic Biopsies and Surgical Tissues.

BACKGROUND: Organoids are three-dimensional in vitro models of human disease developed from benign and malignant gastrointestinal tissues with tremendous potential for personalized medicine applications. We sought to determine whether gastric cancer patient-derived organoids (PDOs) could be safely established from endoscopic biopsies for rapid drug screening. METHODS: Patients underwent esophagogastroduodenoscopy (EGD) for surveillance or staging and had additional forceps biopsies taken for PDO creation. Cancer tissues from operative specimens were also used to create PDOs. To address potential tumor heterogeneity, we performed low-coverage whole-genome sequencing of endoscopic-derived PDOs with paired surgical PDOs and whole-tumor lysates. The stability of genomic alterations in endoscopic organoids was assessed by next-generation sequencing and nested polymerase chain reaction (PCR) assay. The feasibility and potential accuracy of drug sensitivity screening with endoscopic-derived PDOs were also evaluated. RESULTS: Gastric cancer PDOs (n = 15) were successfully established from EGD forceps biopsies (n = 8) and surgical tissues (n = 7) from five patients with gastric adenocarcinoma. Low-coverage whole-genomic profiling of paired EGD and surgical PDOs along with whole-tumor lysates demonstrated absence of tumor heterogeneity. Nested PCR assay identified similar KRAS alterations in primary tumor and paired organoids. Drug sensitivity testing of endoscopic-derived PDOs displayed standard dose-response curves to current gastric cancer cytotoxic therapies. CONCLUSIONS: Our study results demonstrate the feasibility of developing gastric cancer PDOs from EGD biopsies. These results also indicate that endoscopic-derived PDOs are accurate surrogates of the primary tumor and have the potential for drug sensitivity screening and personalized medicine applications.

Prospective clinical trial of Intravitreal aflibercept treatment for PolypoIdal choroidal vasculopathy with hemorrhage or exudation (EPIC study): 6 month results.

BACKGROUND: Polypoidal choroidal vasculopathy is a variant of choroidal neovascularization and neovascular age related macular degeneration presenting with hemorrhagic and exudative changes within the macula and/or peripapillary region leading to vision loss. In contrast to neovascular age related macular degeneration, polypoidal choroidal vasculopathy has differing clinical manifestations and treatment strategies. Historically, polypoidal choroidal vasculopathy complexes are less responsive to anti-vascular endothelial growth factor therapy with no prospective clinical trials evaluating aflibercept in management of polypoidal choroidal vasculopathy. Herein we prospectively evaluate the efficacy and safety of intravitreal aflibercept in polypoidal choroidal vasculopathy. METHODS: A prospective, open-label, investigator-sponsored trial of intravitreal aflibercept for polypoidal choroidal vasculopathy in 21 eyes was conducted. Injections were administered monthly for 3 initial treatments, then every other month with monthly evaluations. The primary outcome measures were the mean change in best corrected visual acuity and adverse events. Secondary outcome measures included stabilization of vision, presence of subretinal hemorrhage, serous detachment, retinal pigment epithelial detachment, and regression of polypoidal complexes on indocyanine green angiography. RESULTS: At 6 months, the median visual acuity was 20/40 (range 20/25-20/200) with a mean Early Treatment Diabetic Retinopathy Study vision of 68.4 letters. There was a gain of 2.76 Early Treatment Diabetic Retinopathy Study letters at 6 months (p = 0.15). No patient developed severe vision loss (≤15 letters) and vision was stable or improved in 19/21 eyes (91 %). Subretinal fluid resolved in 13/18 eyes (72 %), and subretinal hemorrhage resolved in 6/8 eyes (75 %) respectively. The polyps regressed in 14/21 eyes (67 %) and the branching vascular network decreased in 1 eye and was stable in all other eyes. The retinal pigment epithelial detachment improved in 13/15 eyes (87 %). Bimonthly treatment occurred in 15/21 patients (71 %). There were no adverse events. CONCLUSIONS: Intravitreal aflibercept results in stabilization of vision, resolution of exudative and hemorrhagic complications with regression of polyps in polypoidal choroidal vasculopathy. Eyes with polypoidal choroidal vasculopathy previously treated with ranibizumab and bevacizumab can show marked improvement in the retinal pigment epithelial detachments and persistent polyps with aflibercept therapy. TRIAL REGISTRATION: Clinical trials.gov NCT01871376 , June 4(th) 2013.

Open repair of a ruptured abdominal aorta with an aortoiliac vein fistula in a 7-month-old infant and review of the literature.

Ruptured abdominal aortic aneurysms are extremely rare in the pediatric population. In this video case report, we describe the successful repair of a ruptured abdominal aortic aneurysm in a 7-month-old female infant.

Endovascular Solution to Endoleak Phenomenon After Open Repair of Abdominal Aortic Aneurysm.

Endovascular aneurysm repair (EVAR) has quickly outpaced open treatment of infrarenal abdominal aortic aneurysm (AAA) and iliac artery aneurysms, relegating most open AAA repair for either young patients with long life expectancy or patients with extreme anatomic constraints. Typically, open repair involves opening the aneurysm sac with suture ligation of back-bleeding vessels. However, in situations where an aortobifemoral repair is performed, proximal and distal ligation can be performed leaving behind a "remnant" aorta and iliac arteries. Usually, major palpable vessels are ligated and small lumbars spontaneously thrombose. However, failure of this to occur can lead to a rare situation in which there is persistent filling of a remnant aorta and aneurysm sac leading to a situation similar to a type II endoleak after EVAR. Typically, this leak has been repaired by open ligation. We present a technique for endovascular coiling and thrombin injection to correct a "type II endoleak" from a back-bleeding lumbar artery after open aortoiliac and femoral aneurysm repair.

En Face Spectral-Domain Optical Coherence Tomography for the Diagnosis and Evaluation of Polypoidal Choroidal Vasculopathy.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic capability of en face spectral-domain optical coherence tomography (SD-OCT) in patients with polypoidal choroidal vasculopathy (PCV) diagnosed by indocyanine green angiography (ICGA). PATIENTS AND METHODS: A retrospective, consecutive case series of 100 eyes diagnosed with PCV by ICGA were imaged with en face SD-OCT. Evaluation of the PCV complex on en face SD-OCT was performed on the ability to diagnose PCV by the characteristic configuration of the PCV complex and the extent and size of the PCV lesion. RESULTS: The PCV complex was better visualized on ICGA in 45 eyes, on en face SD-OCT in 44 eyes, and equally well in 11 eyes. The extent of the PCV complex was larger on en face SD-OCT in 65 eyes, larger on ICGA in 23 eyes, and equal in size in 12 eyes. CONCLUSION: En face SD-OCT images the characteristic findings of PCV and provides a noninvasive way to diagnose and treat PCV when ICGA is not available. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:737-744.].

Comparing prognostic strength of acute corticospinal tract injury measured by a new diffusion tensor imaging based template approach versus common approaches.

BACKGROUND: Long-term motor outcome of acute stroke patients with severe motor impairment is difficult to predict. While measure of corticospinal tract (CST) injury based on diffusion tensor imaging (DTI) in subacute stroke patients strongly predicts motor outcome, its predictive value in acute stroke patients is unclear. Using a new DTI-based, density-weighted CST template approach, we demonstrated recently that CST injury measured in acute stroke patients with moderately-severe to severe motor impairment of the upper limb strongly predicts motor outcome of the limb at 6 months. NEW METHOD: The current study compared the prognostic strength of CST injury measured in 10 acute stroke patients with moderately-severe to severe motor impairment of the upper limb by the new density-weighted CST template approach versus several variants of commonly used DTI-based approaches. RESULTS AND COMPARISON WITH EXISTING METHODS: Use of the density-weighted CST template approach yielded measurements of acute CST injury that correlated most strongly, in absolute magnitude, with 6-month upper limb strength (rs=0.93), grip (rs=0.94) and dexterity (rs=0.89) compared to all other 11 approaches. Formal statistical comparison of correlation coefficients revealed that acute CST injury measured by the density-weighted CST template approach correlated significantly more strongly with 6-month upper limb strength, grip and dexterity than 9, 10 and 6 of the 11 alternative measurements, respectively. CONCLUSIONS: Measurements of CST injury in acute stroke patients with substantial motor impairment by the density-weighted CST template approach may have clinical utility for anticipating healthcare needs and improving clinical trial design.

Corticospinal tract diffusion abnormalities early after stroke predict motor outcome.

BACKGROUND: Prognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine. OBJECTIVE: Our primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume. METHODS: In all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured. RESULTS: Acute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures. CONCLUSIONS: Loss in acute CST AD and subacute CST FA are strong prognostic indicators of future motor functions of the upper limb for stroke patients with substantial initial motor impairment. DTI-derived measure of CST injury early after stroke may have utility in health care planning and in design of acute stroke clinical trials.