Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.

A retrospective study of patients with surgically resectable adenocarcinoma of the pancreatic head was undertaken to determine which prognostic factors are independently associated with improved survival. Thirty-four men and 41 women (mean age, 61.9 years) had resection for adenocarcinoma of the pancreatic head between 1980 and 1997 at Rush-Presbyterian-St. Luke's Medical Center. Surgical resections included 15 total pancreatectomies, 43 pyloric-preserving procedures, and 17 standard Whipple procedures. Thirty-six patients received adjuvant radiation and/or chemotherapy. Overall median survival was 13 months, with a 5-year survival of 17 per cent. Thirty-day surgical mortality was 1.3 per cent. Significant factors that negatively influenced survival using univariate Kaplan-Meier analysis were: positive resection margin (P = 0.01), intraoperative blood transfusion (P = 0.01), and lymph node metastases (P = 0.01). Presenting signs and symptoms, patient demographics, operative procedure, tumor size, histologic differentiation, and adjuvant therapy did not have a significant impact on survival. Using multivariate Cox regression analysis, the only significant independent factors improving survival were the absence of intraoperative blood transfusion (P = 0.02) and a negative resection margin (P = 0.04). Performing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas with negative microscopic margins of resection and without intraoperative transfusion significantly improves survival.

The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell–cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER⁺/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified nearHLA-Aand were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.

Objective: To evaluate the effect of surgical approach and adjuvant therapy on patients with carcinoma of the esophagus and/or cardia. Design: Retrospective analysis of 157 consecutive patients who underwent esophagectomy. Setting: A private university medical center and its affiliated community hospital. Patients: One hundred twenty men and 37 women (mean age, 61.7 years) with carcinoma of the esophagus and/or cardia that was surgically treated between 1978 and 1993. Interventions: Three approaches were used for resection: Transhiatal esophagectomy (THE) (n=67), transthoracic esophagectomy (TTE) (n=71), and abdominalonly esophagectomy (AOE) (n=19). Sixty-five patients received adjuvant radiotherapy and chemotherapy. Main Outcome Measures: Surgical mortality, morbidity, and survival and the effect of adjuvant therapy. Results: The overall surgical mortality rate was 7.6%: 12.7% with the TTE, 4.5% with the THE, and 0% with the AOE approach. A significantly increased incidence of adult respiratory distress syndrome (P<.001) and empyema (P<.001) was seen with the TTE approach. The average intraoperative blood loss (P=.08) and the median intensive care unit stay (P=.26) and hospital stay (P=.40) were decreased with the THE and AOE approaches when compared with the TTE approach without significance. The overall median survival time was 17 months, with a 5-year survival rate of 21%. There was no significant difference in survival by pathologic stage between approaches. The addition of adjuvant therapy did not affect the overall median survival time or the 5-year survival rate. Node-positive patients did benefit from adjuvant radiotherapy and chemotherapy, with increased median survival times from 7 to 15 months and a 5-year survival rate from 0% to 15% (P=.01). Conclusions: The THE and AOE approaches have fewer early complications than does TTE. Both THE and TTE have equal long-term survival rates. Adjuvant therapy provides increased survival to node-positive patients with carcinoma of the esophagus and/or cardia. (Arch Surg. 1995;130:617-624)