Workload, Recurrence, Quality of Life and Long-term Efficacy of Endoscopic Therapy for High-grade Dysplasia and Intramucosal Esophageal Adenocarcinoma.

OBJECTIVE: To review the workload, type and frequency of recurrence, long-term quality of life (QOL), and late oncologic outcomes with endoscopic therapy. BACKGROUND: The short-term oncologic efficacy of endoscopic resection (ER) and ablation for patients with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC) is well-established in the literature. METHODS: A retrospective chart review was performed of the initial 40 patients who had endoscopic therapy from 2001 to 2010 at 1 center by 1 physician. RESULTS: Initial pathology was HGD in 22 and IMC in 18 patients, but 9 patients (41%) with HGD progressed to invasive cancer during endotherapy. The median follow-up was 82 months. Four patients had an esophagectomy, and in the remaining 36 patients, 70 ERs and 111 ablations were performed. The median number of endoscopic sessions was 4 in patients with short segment compared with 7 in patients with long-segment Barrett's. Complete resolution of intestinal metaplasia (CRIM) was achieved in 30 patients (83%) at a median of 21 months. In 18 patients (60%), CRIM was maintained, whereas 12 patients developed recurrence at a median of 14 months. Additional endotherapy (n = 11) led to CRIM again in 10 patients (83%). There were no cancer deaths when CRIM was achieved. Overall survival with endotherapy was 73% at 5 years and 67% at 10 years. Quality of life (QOL) was below population means in 4 of 8 areas, but alimentary satisfaction was good after endotherapy. CONCLUSIONS: Endotherapy is successful in most patients, but multiple sessions are usually required and disease progression can occur. Once CRIM is achieved, recurrence is common and mandates continued endoscopic follow-up. QOL is impaired with endotherapy, but alimentary satisfaction and oncologic outcomes support esophageal preservation with endotherapy for patients with HGD or IMC.

Clinical outcome after laparoscopic Nissen fundoplication in patients with GERD and PPI refractory heartburn.

Typical reflux symptoms that respond well to proton pump inhibitor (PPI) therapy are key factors predictive of an excellent outcome with antireflux surgery for gastroesophageal reflux disease (GERD). Our aim was to evaluate whether poor preoperative heartburn (HB) relief with PPIs was associated with a worse outcome after Nissen fundoplication. Patients with a main symptom of HB and a positive pH-test who had a laparoscopic Nissen fundoplication between January 2008 and December 2014 were included. Prior to surgery, patients graded how effectively their HB symptoms were relieved by PPIs. Three groups were defined: good response (76-100% relief), partial response (26-75% relief) and poor response (0-25% relief). Outcomes and satisfaction were assessed at a minimum of 1 year after fundoplication. There were 129 patients who met inclusion criteria and 75 agreed to participate. The median follow-up was 48 months. Prior to Nissen fundoplication 13 patients had a good HB response to PPI-therapy, 36 had a partial response and 26 had a poor response. All patients were satisfied with their HB relief after fundoplication (mean satisfaction score: 9.5/10) and there was no difference in satisfaction score or heartburn relief between groups. Heartburn symptoms that respond poorly to PPI therapy are reliably relieved with a Nissen fundoplication in patients with objectively confirmed GERD. Patient satisfaction after Nissen fundoplication was excellent and was similar in patients with poor versus excellent HB relief with preoperative PPI therapy. Therefore, antireflux surgery is an option for patients with HB and confirmed GERD regardless of the degree of relief of HB symptoms provided by PPI medications.

Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma.

BACKGROUND: Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC). METHODS: This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy. RESULTS: There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4-8.0), and the median number of resected nodes was 48 (23-85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%. CONCLUSIONS: Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.

Gastric cancer in the young: An advanced disease with poor prognostic features.

BACKGROUND AND OBJECTIVES: Gastric cancer in young patients is rare. We analyzed the clinicopathological features and prognosis of early-onset gastric carcinoma. METHODS: We retrospectively reviewed patients with gastric adenocarcinoma aged ≤45 years and >45 years at our institution over a 17-year period. Clinicopathological features were compared and survival analysis was performed using Kaplan-Meier curves. RESULTS: A total of 121 patients with gastric carcinoma aged ≤45 years were identified. The young group (YG) had a higher incidence of stage III/IV disease (86.8% vs. 57.9%, P < 0.001), poorly-differentiated carcinoma (95.9% vs. 74.4%, P < 0.001), and signet-cell type tumor (88.4% vs. 32.2%, P < 0.001) relative to the older group (OG). The majority of tumors were in the middle third of the stomach in both groups (P = 0.108). Three-year survival in the YG was 87.1%, 32.2%, and 6.9% in stage I/II, III, and IV disease, respectively. Surgical intervention in young patients with advanced carcinoma was not associated with improved survival. Although median survival was shorter in the YG compared to the OG (11.7 vs. 41.0 months, P < 0.001), stage-specific survival was similar. CONCLUSION: Early-onset gastric cancer demonstrates advanced stage of disease, and a high incidence of poorly-differentiated and signet-cell type carcinoma. Overall survival is poor with no added benefit to surgical intervention in advanced disease.

Intraoperative methadone for day-case gynaecological laparoscopy: A double-blind, randomised controlled trial.

Optimal pain relief in day-case surgery is imperative to patient comfort and timely discharge from hospital. Short-acting opioids are commonly used for analgesia in modern anaesthesia, allowing rapid recovery after surgery. Plasma concentration fluctuations from repeated dosing of short-acting opioids can cause patients to oscillate between analgesia with potential adverse effects, and inadequate analgesia requiring rescue dosing. Methadone's unique pharmacology may offer effective and sustained analgesia with less opioid consumption, potentially reducing adverse effects. Using a double-blind, randomised controlled trial, we compared post-anaesthesia care unit opioid consumption between day-case gynaecological laparoscopy patients who received either intravenous methadone (10 mg), or short-acting opioids intraoperatively. The primary outcome was post-anaesthesia care unit opioid consumption in oral morphine equivalents. Secondary outcomes included total opioid consumption, discharge opioid consumption, pain scores (0-10) until discharge, adverse effects (respiratory depression, postoperative nausea and vomiting, excess sedation), and rate of admission. Seventy patients were randomly assigned. Patients who received methadone consumed on average 9.44 mg fewer oral morphine equivalents in the post-anaesthesia care unit than the short-acting group (18.02 mg vs 27.46 mg, respectively, 95% confidence interval 0.003 to 18.88, P = 0.050) and experienced lower postoperative pain scores at every time point, although absolute differences were small. There was no evidence of lower hospital or discharge opioid consumption. No significant differences between the methadone and short-acting groups in other outcomes were identified: respiratory depression 41.2% versus 31.4%, Padjusted >0.99; postoperative nausea and vomiting 29.4% versus 42.9%, Padjusted >0.99; overnight admission 17.7% versus 11.4%, Padjusted >0.99; excess sedation 8.82% versus 8.57%, Padjusted >0.99. This study provides evidence that, although modestly, methadone can reduce post-anaesthesia care unit opioid consumption and postoperative pain scores after day-case gynaecological laparoscopy. There were no significant differences in any secondary outcomes.

A Case Report of Unilateral Syphilitic Uveitis: A Diagnostic Challenge and the Role of Point-of-care Ultrasound.

Introduction: Syphilis presents with diverse clinical manifestations, posing challenges for diagnosis, especially in the fast-paced emergency department (ED) setting. Case Report: We report a rare case of unilateral syphilitic uveitis in an individual who had been sexually abstinent for 13 years. Using ocular point-of-care ultrasound in the ED, we successfully diagnosed this uncommon ocular manifestation. Conclusion: Our case highlights the diagnostic challenges of ocular syphilis and emphasizes the crucial nature of timely identification. Collaborative efforts with specialties such as ophthalmology are essential in overcoming these challenges.

Retained polyvinyl chloride fragments in the cornea following trauma.

Purpose: PVC is a synthetic plastic polymer used worldwide for a wide range of applications. While it is often associated with ocular trauma, little is known regarding how PVC may interact with ocular tissues. Herein we report the clinical course of a patient with polyvinyl chloride (PVC) embedded in the cornea after a projectile injury, utilizing anterior segment optical tomography to study the relative antigenicity and reactivity of this industrial material in the cornea. Observations: A 29-year-old male presented with acute, unilateral vision loss in the left eye following ocular trauma while working with PVC. On exam, he had a near full-thickness corneal laceration with multiple small fragments of PVC in the corneal stroma. Given the small size and depth of the fragments, the patient was medically managed with close follow-up. After 6 days, his visual acuity returned to baseline and the corneal laceration was found to be well healed. Anterior OCT imaging identified discrete, individual fragments and there was no associated inflammatory response. At 3 months, the patient continued to do well with no signs of ocular inflammation. Conclusions and Importance: PVC is a commonly used plastic in workplace settings that pose a risk for projectile injuries to the eye. This case highlights that at least in the short-term, PVC appears to be inert in the corneal stroma, allowing for medical management and close follow-up, rather than surgical removal.

The Performance and Reception of Race-Based Athletic Activism: Toward a Critical, Dramaturgical Theory of Sport.

The emergence of an unprecedented wave of race-based athletic activism in the last decade presents the opportunity to formulate a more critical, cultural theory of the significance and socio-political function of sport in contemporary life. We begin by centering athlete agency and highlighting the distinctive performative, communicative, and symbolic opportunities that sport affords. However, athletic activism and social messaging are also structured-and their impacts shaped-by a range of contextual factors and institutional forces as well as sport's own unique cultural status and ideological claims. We catalog these constraints to capture the larger cultural field of sport as a site of racial commentary and contestation. Situating this multifaceted field of protest and response in its larger social, cultural, and media contexts leads us to argue that sport presents a vehicle not only for the performance of protest (as existing theory might have it), but for the representation and dramatization of social contestation, struggle, and change more generally. The lessons and broader implications of this synthesis are discussed in the conclusion.

Schizophrenia in Translation: Why the Eye?

Schizophrenia is increasingly recognized as a systemic disease, characterized by dysregulation in multiple physiological systems (eg, neural, cardiovascular, endocrine). Many of these changes are observed as early as the first psychotic episode, and in people at high risk for the disorder. Expanding the search for biomarkers of schizophrenia beyond genes, blood, and brain may allow for inexpensive, noninvasive, and objective markers of diagnosis, phenotype, treatment response, and prognosis. Several anatomic and physiologic aspects of the eye have shown promise as biomarkers of brain health in a range of neurological disorders, and of heart, kidney, endocrine, and other impairments in other medical conditions. In schizophrenia, thinning and volume loss in retinal neural layers have been observed, and are associated with illness progression, brain volume loss, and cognitive impairment. Retinal microvascular changes have also been observed. Abnormal pupil responses and corneal nerve disintegration are related to aspects of brain function and structure in schizophrenia. In addition, studying the eye can inform about emerging cardiovascular, neuroinflammatory, and metabolic diseases in people with early psychosis, and about the causes of several of the visual changes observed in the disorder. Application of the methods of oculomics, or eye-based biomarkers of non-ophthalmological pathology, to the treatment and study of schizophrenia has the potential to provide tools for patient monitoring and data-driven prediction, as well as for clarifying pathophysiology and course of illness. Given their demonstrated utility in neuropsychiatry, we recommend greater adoption of these tools for schizophrenia research and patient care.

OCT and OCT Angiography Offer New Insights and Opportunities in Schizophrenia Research and Treatment.

The human retina and retinal imaging technologies continue to increasingly gain the attention of schizophrenia researchers. With the same embryologic origin as the brain, the retina offers a window into neurovascular changes that may underlie disease. Recently, two technologies that have already revolutionized the field of ophthalmology, optical coherence tomography (OCT), and a functional extension of this, optical coherence tomography angiography (OCTA), have gained traction. Together, these non-invasive technologies allow for microscopic imaging of both structural and vascular features of the retina. With ease of use and no side effects, these devices are likely to prove powerful digital health tools in the study and treatment of schizophrenia. They may also prove key to discovering disease relevant biomarkers that underly neurodevelopmental and neurodegenerative aspects of conditions such as schizophrenia.

Retinal Microvasculature in Schizophrenia.

PURPOSE: Schizophrenia is associated with alterations in neural structure and function of the retina that are similar to changes seen in the retina and brain in multiple neurodegenerative disorders. Preliminary evidence suggests that retinal microvasculature may also be compromised in schizophrenia. The goal of this study was to determine, using optical coherence tomography angiography (OCTA), whether 1) schizophrenia is associated with alterations in retinal microvasculature density; and 2) microvasculature reductions are associated with retinal neural layer thinning and performance on a measure of verbal IQ. PATIENTS AND METHODS: Twenty-eight outpatients with schizophrenia or schizoaffective disorder and 37 psychiatrically healthy control subjects completed OCT and OCTA exams, and the Wechsler Test of Adult Reading. RESULTS: Schizophrenia patients were characterized by retinal microvasculature density reductions, and enlarged foveal avascular zones, in both eyes. These microvascular abnormalities were generally associated with thinning of retinal neural (macular and peripapillary nerve fiber layer) tissue (but the data were stronger for the left than the right eye) and lower scores on a proxy measure of verbal IQ. First- and later-episode patients did not differ significantly on OCTA findings. CONCLUSION: The retinal microvasculature impairments seen in schizophrenia appear to be a biomarker of overall brain health, as is the case for multiple neurological conditions. Additional research is needed, however, to clarify contributions of social disadvantage and medical comorbidities to the findings.

Quantifying Subclinical and Longitudinal Microvascular Changes Following Episcleral Plaque Brachytherapy Using Spectral Domain-Optical Coherence Tomography Angiography.

PURPOSE: To assess longitudinal microvascular changes in eyes treated with I-125 episcleral plaque brachytherapy (EPB). METHODS: High resolution OCT angiograms of the central 3×3mm macula were obtained from I-125 episcleral plaque brachytherapy treated and untreated fellow eyes of 61 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics. RESULTS: At 6 months, treated eyes had significantly lower VSD (0.145 ± 0.003 vs 0.155 ± 0.002; p = 0.009) and higher FIR (2.01 ± 0.199 vs 1.46 ± 0.104; p = 0.010) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.92 ± 0.025 vs 2.84 ± 0.018; p < 0.001). When our cohort was categorized into low dose radiation (<15Gy) and high dose radiation (>45Gy) to the fovea, there were significant differences in VSD and FIR between groups. CONCLUSIONS: OCTA can be used to quantify and monitor EPB induced retinopathy, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.

Bilateral Choroidal Neovascularization and Chorioretinal Anastomosis in Autosomal Recessive Bestrophinopathy.

Purpose: This case report discusses a case of bilateral chorioretinal anastomoses in autosomal recessive bestrophinopathy (ARB) unresponsive to antivascular endothelial growth factor therapy and its associated optical coherence tomography angiography (OCTA) findings. Methods: An observational case report is presented. Results: An 8-year-old girl initially presented at age 2 years with multifocal midperipheral yellow subretinal deposits with intraretinal and subretinal fluid. She was treated with intravitreal injections of bevacizumab in both eyes with minimal response. OCTA revealed the presence of choroidal neovascularization and chorioretinal anastomoses. Molecular diagnosis of ARB was achieved with the identification of compound heterozygous mutations in BEST1, including a silent exonic splicing mutation. Conclusions: Subretinal or intraretinal fluid in ARB may be exacerbated by the presence of chorioretinal anastomosis detected on OCTA. Silent exonic mutations that cause no amino acid change can be overlooked but are pathogenic in ARB.

Impaired Retinal Vascular Reactivity in Diabetic Retinopathy as Assessed by Optical Coherence Tomography Angiography.

Purpose: To assess retinal vascular reactivity in healthy controls and subjects with diabetic retinopathy (DR). Methods: A total of 22 healthy control eyes and 16 eyes with DR were enrolled. Images were acquired using a commercially available swept-source optical coherence tomography angiography (SS-OCTA) system. Three conditions were tested for each patient (hyperoxia, hypercapnia, and room-air) by employing a non-rebreathing apparatus that delivered appropriate gas mixtures (100% O2, 5% CO2, room air). Vessel skeleton density (VSD) and vessel diameter index (VDI) were compared between the conditions using mixed-model ANOVA adjusting for age and hypertension. Significant gas or interaction effects were followed by a Bonferroni adjusted pairwise post hoc analysis. Statistical significance was defined at P < 0.05. Results: The mixed-model ANOVA of the VSD found a significant intraindividual gas effect (F[2, 70] = 20.3, P < 0.001) and intergroup effect (F[1, 35] = 6.9, P = 0.001), and interaction effects (F[2, 70] = 4.6, P = 0.03). The post hoc pairwise comparison found significant differences among all three gas conditions in the healthy controls. In the subjects with DR, there were significant differences in VSD between hyperoxic and room air, and between hyperoxic and hypercapnic conditions, but not between hypercapnic and room-air conditions. Similar results were found for VDI. Conclusions: The retinal capillaries, assessed with SS-OCTA, in subjects with DR preferentially reacted to hyperoxia but not hypercapnia, while the healthy controls reacted to both. The difference in the vascular reactivity may be indicative of the underlying pathophysiology of DR.

Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies.

OBJECTIVE: To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD). METHODS: Patients with extra-vascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extra-vascular motion signal on OCTA were named "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face OCTA images (3mm × 3mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and its corresponding hyperreflective fluid. Longitudinal data were collected when available. MAIN OUTCOME MEASURES: Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom. RESULTS: Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated; 60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy. Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate similar OCTA signal. SSPiM showed an anatomic preference for vascular-avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In five of eight longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images. CONCLUSIONS: Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.

Esophageal adenocarcinoma stage III: Survival based on pathological response to neoadjuvant treatment.

BACKGROUND: Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal adenocarcinomas (EAC). Pathological response is thought to be a major prognostic factor. Aims of this study were to determine the frequency of complete response and to compare the survival of complete and incomplete responders in stage III EAC. METHODS: A retrospective review was performed of all stage III patients that underwent neoadjuvant therapy followed by esophagectomy between 1999 and 2015. Patients were classified into complete (pCR) versus incomplete responders (pIR). RESULTS: 110 patients were included. Neoadjuvant chemotherapy was applied in 25 (23%) and chemoradiotherapy in 85 (77%) patients. Pathologic response was complete in 25% (n = 27) and was more common after chemoradiotherapy. Mean F/U interval was 36 months (0.3-173). There was a significant difference in the overall survival between complete and incomplete responders (p = 0.036). Median survival in the pIR group was 24.4 months and the median survival was not reached during the observation time in pCR. The 3-year-survival-rate was 70% in pCR and 40% in pIR (p = 0.01). Positive lymph nodes (ypN+) were present in 56 patients (51%). The 3-year-survival-rate was 59% in pIR with ypN0 and 29% in pIR with ypN+ (p = 0.005). CONCLUSIONS: Complete response to neoadjuvant therapy has a significantly better overall and 3-year-survival after esophagectomy than incomplete response. In incomplete responders, residual lymph node disease was associated with a significantly worse survival. These findings suggest that the degree of pathologic response and lymph node status are major prognostic factors for survival in EAC patients with stage III disease.