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Background Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma. The limited disease-free survival after chemotherapy has resulted in a poor prognosis. The outcomes data for high-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) for PEL are limited owing to the rarity of the disease. Patients and Methods The present study included 9 patients with PEL from 2 major academic centers. Of these patients, 4 had received auto-HCT after high-dose therapy. Of the 9 patients, 8 (89%) had immunodeficiency (7 with human immunodeficiency virus seropositivity; 1, a solid organ transplant recipient) at the diagnosis. Human herpesvirus-8 by immunohistochemistry was positive in 8 patients. Anthracycline-based combination chemotherapy was used as first-line treatment in 7 patients; 4 underwent auto-HCT after attaining first complete remission. Results The median follow-up of the surviving patients was 25 months (95% confidence interval [CI], 8%-29%). The 2-year progression-free and overall survival for the 8 patients who had received treatment was 58% (95% CI, 22%-95%) and 73% (95% CI, 41%-100%), respectively. The 2-year progression-free and overall survival for the patients who had received auto-HCT was 50% (95% CI, 1%-99%) and 75% (95% CI, 33%-100%), respectively. Of the 4 auto-HCT recipients, all had been in first complete remission at the time of autografting. The cumulative incidence of relapse was 50% (95% CI, 19%-100%). No deaths were attributable to auto-HCT at 2 years after autografting. Conclusion Despite the small sample size, our data have shown that consolidative auto-HCT is safe and effective and should be considered for eligible patients with PEL after demonstration of an objective response to induction chemotherapy. However, the high relapse rate remains a concern and warrants the development of new strategies to mitigate post-transplantation relapse.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices. Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons. Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004). Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results. Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.

Primary effusion lymphoma (PEL) is a rare AIDS-associated non-Hodgkin lymphoma, growing in the serous body cavities as a lymphomatous effusion. The endoscopic features of PEL can mimic Kaposi sarcoma (KS). We present a case where PEL presented as small intestinal masses which had a similar macroscopic appearance to KS. Endoscopic evaluation was used with biopsies which confirmed the diagnosis of PEL. PEL is a differential of gastrointestinal KS. Accurate diagnosis is crucial for prognostication in these patients. Our case emphasizes that PEL presenting as intestinal tumors can mimic KS macroscopically. Although treatment for PEL and KS includes standard chemotherapy with concurrent antiretroviral therapy, early detection of PEL can improve overall survival in these patients.

Background and Aims The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. Methods Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. Results One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. Conclusions In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

ObjectiveSurveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines.DesignData on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies.Results594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4–4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI −7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia).ConclusionsBE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Introduction Surveillance intervals and biopsy protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett’s oesophagus (BO) are intensive and not based on substantial evidence. We aimed to assess the timeline, location, and histology of recurrence following CRIM with the goal of assessing the appropriateness of current recommendations. Methods Data on patients undergoing RFA for BO-related neoplasia were obtained from prospectively maintained databases of five (3 USA and 2 UK) tertiary referral centres with expertise in management of BO-related neoplasia. Patients underwent RFA following endoscopic mucosal resection (EMR) of visible lesions. RFA was performed every three months till CRIM was confirmed endoscopically and histologically on two consecutive endoscopies. Subsequent surveillance was performed at 3, 6, 9, and 12 months thereafter. Recurrence incidence was estimated using Kaplan-Meier method and Cox Proportional Hazards models were used to assess predictors of recurrence. Results 594 patients achieved CRIM as of April 1 st 2017 and were included in the analysis. Mean (standard deviation (SD)) age was 67 (10) years and 86% were males. Median (interquartile range (IQR)) BO segment length was 4 (2–6) cm. 90% of patients were treated for dysplasia or carcinoma. 151 subjects developed recurrent BO over a median (IQR) follow up of 2.8 (1.4–4.4) years. BO recurred at the gastroesophageal junction (GOJ) in 67% of subjects and in the tubular oesophagus in 33%. 84% of BO recurrences in the tubular oesophagus occurred within 5 cm of the GOJ. Histology of recurrences included cancer (9%), high grade dysplasia (HGD) (8%), low grade dysplasia (LGD) (12%), indefinite for dysplasia (2%) and non-dysplastic BO (69%). Annual incidence of any recurrence was 9.6%, dysplastic (LGD/HGD/cancer) recurrence was 2.8% and HGD/Cancer recurrence was 1.6%. The recurrence hazard rate did not vary over the follow-up (p=0.74) with 19% risk within 2 years and an additional 49% risk over the next 8.6 years. Recurrence hazard rate of any dysplasia and HGD/Cancer while lower, also did not vary over the duration of follow up (p=0.94 and p=0.88, respectively) (Figure 1). In a multivariable model, baseline HGD/cancer predicted recurrence (hazard ratio 1.9, 95% CI 1.2–3.1, p=0.004). Conclusions In this large multicentre and international cohort study, BO recurrence risk (at least in the first 5 years following CRIM) did not appear to vary over time suggesting that continued surveillance remains important. Most recurrences appear to occur at the GOJ or distal 5 cm of the oesophagus. Sampling the GOJ and the distal 5 cm of the oesophagus in the absence of visible lesions may be adequate for surveillance.

Background The neo-squamous epithelium that replaces columnar epithelium after successful endoscopic ablation of Barrett's esophagus (BE) has not been fully characterized in regard to its structural and functional integrity. Intercellular space is a surrogate marker for epithelial structural integrity and mucosal impedance (MI) is a surrogate for transepithelial resistance and thus epithelial functional integrity. Impairment of the structural and functional integrity may influence recurrence following successful ablation. We aimed to measure the esophageal epithelial intercellular space diameter and MI in the neo-squamous and normal squamous epithelium of patients who underwent successful radiofrequency ablation for dysplastic BE. Methods Forty patients with complete remission of intestinal metaplasia (CRIM) (defined as two negative surveillance endoscopies for intestinal metaplasia) were prospectively recruited. Patients were excluded if they had endoscopic evidence of esophagitis. MI measurements were taken at 1 cm above the GE junction and 2 cm above the prior BE segment (targeting uninvolved squamous epithelium), using a novel through the scope MI probe. Endoscopic biopsies were also taken at these corresponding sites to assess intercellular space diameter using transmission electron microscopy (TEM) using standard techniques. Results 80% of patients were male with a mean age of 69 years. Mean follow since achieving CRIM was 30 months. 39 patients underwent RFA for dysplasia. The mean intercellular space diameter was higher in the neo-squamous epithelium (1.01 μm) when compared to the untreated native squamous epithelium (0.96 μm) [Difference of 0.056 μm, 95% CI of -0.036 to 0.148, P = 0.228]. The mean MI was significantly lower in the neosquamous epithelium (4001.3 Ω) when compared to the untreated native epithelium (5168.1 Ω) [Difference of 1166.7 Ω, 95% CI 418.8 to 1914.6, P = 0.003]. Conclusion Neo-squamous epithelium that replaces BE epithelium following successful endoscopic therapy for BE appears to be functionally and likely structurally deficient with regards to acid reflux barrier function, when compared to native squamous esophageal epithelium. This impairment may be associated with recurrence following successful ablation. Disclosure All authors have declared no conflicts of interest.