Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). RESULTS: Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. CONCLUSIONS: Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement. TRIAL REGISTRATION NUMBER: NCT03656380.

Concordant, non-atypical breast papillomas do not require surgical excision: A 10-year multi-institution study and review of the literature.

PURPOSE: Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature. MATERIALS AND METHODS: Following IRB approval, CNB results from Duke University (7/1/2004-6/30/2014) and the University of North Carolina Chapel Hill (1/1/04-6/30/2013) were reviewed to identify non-atypical papillomas. All cases with surgical excision or 2 years of imaging follow up were included. In addition, a literature review identified 60 published studies on upgrades of NAPs diagnosed at CNB. Cases in our cohort and the published literature were reviewed for confounding factors: [1] missing radiologic-pathologic concordance and/or discordance, [2] papillomas included with high-risk lesions, [3] high risk lesions counted as upgrades, [4] review by a nonspecialized breast pathologist, and [5] cancer incidentally detected. RESULTS: Of the 388 CNBs in our dual-institution cohort, 136 (35%) patients underwent surgical excision and 252 (65%) patients had imaging follow up. After controlling for confounders, no cancers (0/388) were found at surgical excision or during follow up imaging. The literature review upstaging rate was 4.0% (166/4157) but 1.8% (4/227) after excluding studies with confounders. The combined upstaging rate from the literature and this study was 0.6% (4/615). CONCLUSION: The upstaging rate for CNB diagnosed NAPs was 0% in our cohort and 0.6% overall after adjusting for confounders. This low rate does not warrant reflexive surgical excision and diagnostic imaging follow up should be discretionary.

Hepatocellular Carcinoma, Virilization, and Hilus Cell Hyperplasia in a Girl With Turner Syndrome.

Patients with Turner syndrome (TS) are known to be at risk for excess androgen production and virilization associated with gonadoblastoma and Y chromosome mosaicism, and excess androgens are a risk factor for the development of hepatocellular carcinoma. However, virilization and hepatocellular carcinoma have not been described in a patient with TS. A 10-year-old with nonmosaic 45,X TS presented with clitoromegaly, accelerated linear growth velocity, advanced bone age, and elevated testosterone levels as well as a second occurrence of hepatocellular carcinoma. Gonadectomy was performed, and pathology revealed hilus cell hyperplasia. Immunohistochemical staining of both the original and recurrent hepatocellular carcinoma tissues was diffusely positive for androgen receptors. After gonadectomy, testosterone levels were measurable but normal, with no further virilization; however, the liver mass continued to grow. Ovarian hilus cell hyperplasia should be considered a potential etiology for virilization in the TS population. Excess endogenous testosterone exposure in girls and women with TS may be associated with hepatocellular carcinoma expressing the androgen receptor, though normalizing testosterone levels may not lead to tumor regression in these cases.

Management of Serrated Polyps of the Colon.

PURPOSE OF REVIEW: The purpose of this review is to summarize the management of serrated colorectal polyps (SPs), with a particular focus on the most common premalignant SP, sessile serrated adenoma or polyp (SSA/P). These lesions present a challenge for endoscopists with respect to detection and resection, and are also susceptible to pathologic misdiagnosis. RECENT FINDINGS: Patients with SSA/Ps are at an increased risk of future colorectal neoplasia, including advanced polyps and cancer. Reasonable benchmarks for SP detection rates are 5-7% for SSA/Ps and 10-12% for proximal SPs. Certain endoscopic techniques such as chromoendoscopy, narrow band imaging, water immersion, and wide-angle viewing may improve SSA/P detection. Emerging endoscopic techniques such as underwater polypectomy, suction pseudopolyp technique, and piecemeal cold snare polypectomy are helpful tools for the endoscopist's armamentarium for removing SSA/Ps. Proper orientation of SSA/P specimens can improve the accuracy of pathology readings. Patients with confirmed SSA/Ps and proximal HPs should undergo surveillance at intervals similar to what is recommended for patients with conventional adenomas. Patients with SSA/Ps may also be able to lower their risk of future polyps by targeting modifiable risk factors including tobacco and alcohol use and high-fat diets. NSAIDs and aspirin appear to be protective agents. SPs and SSA/Ps in particular are important colorectal cancer precursors that merit special attention to ensure adequate detection, resection, and surveillance.

Immunoglobulin G4-Related Lymphadenopathy.

Immunoglobulin G4-related lymphadenopathy (IgG4-RLAD) occurs in the setting of extranodal IgG4-related disease (IgG4-RD), an immune-mediated process described in many organ systems characterized by lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells and fibrosis. Although the morphologic features in the lymph node sometimes resemble those seen at the extranodal sites, 5 microscopic patterns have been described, most of which resemble reactive lymphoid hyperplasia. This morphologic variability leads to unique diagnostic challenges and a broad differential diagnosis. As IgG4-RD may be exquisitely responsive to steroids or other immunotherapy, histologic recognition and inclusion of IgG4-RLAD in the differential diagnosis is vital.