A spatially resolved single-cell genomic atlas of the adult human breast.

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide a reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.

A spatially resolved single cell genomic atlas of the adult human breast.

The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While previous studies have mainly focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 535,941 cells from 62 women, and 120,024 nuclei from 20 women, identifying 11 major cell types and 53 cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Our spatial mapping using three technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells in the ducts and lobules, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of adult normal breast tissue for studying mammary biology and disease states such as breast cancer.

Direct Endoscopic Necrosectomy With and Without Hydrogen Peroxide for Walled-off Pancreatic Necrosis: A Multicenter Comparative Study.

INTRODUCTION: Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage. METHODS: Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery. RESULTS: Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P < 0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30). DISCUSSION: H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).

Secondary Causes of Hypertriglyceridemia are Prevalent Among Patients Presenting With Hypertriglyceridemia Induced Acute Pancreatitis.

BACKGROUND: Hypertriglyceridemia induced acute pancreatitis (HIAP) is the third common cause of acute pancreatitis. HIAP can result in recurrent attacks of severe AP with significant morbidity and mortality. Hypertriglyceridemia (HTG) could be primary or secondary. Although genetic causes of HTG are well studied, the prevalence of secondary causes of HTG in patients presenting with HIAP is not well characterized. This study aimed to identify the prevalence of risk factors for secondary hypertriglyceridemia among patients presenting with HIAP in a tertiary referral center in a large metropolitan area. METHODS: This is a retrospective analysis of all patients admitted with AP from August 2012-2017. A subgroup of patients with triglycerides >880 mg/dl were included for analysis. Secondary causes of HTG were identified. Secondary analysis evaluating the severity of pancreatitis was performed. RESULTS: There were 3,746 patients admitted for AP of which 57 patients had AP and HTG. Of these 57 patients, 70.2% had history of diabetes mellitus, 26.3% had history of heavy alcohol use, 22.8% had chronic kidney disease, 47.3% with obesity, and 21.1% with metabolic syndrome. Two patients were classified as unexplained HTG. Secondary analysis showed a total of 45.6% of patients requiring ICU admission. 26.3% of patients with severe inflammatory pancreatitis and 17.5% of patients with severe necrotizing pancreatitis. CONCLUSIONS: In our cohort of HIAP, 55 out of 57 patients had secondary causes for HTG. Identifying secondary causes of HTG during acute hospitalization is important to tailor outpatient treatment in order to prevent future admissions with HIAP.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. METHODS: We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. RESULTS: Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. CONCLUSIONS: ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.