Risk factors for progression of low-grade dysplasia in patients with Barrett's esophagus.

BACKGROUND & AIMS: Data vary on the progression of low-grade dysplasia (LGD) in patients with Barrett's esophagus (BE); in patients with LGD, we investigated the incidence of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) and compared progression in patients with different forms of LGD (prevalent vs incident and multifocal vs unifocal). We assessed the effects of consensus diagnosis of LGD on progression rates to HGD and EAC among expert pathologists. METHODS: In a multicenter outcomes project, 210 patients with BE and LGD (classified as incident, prevalent, or persistent) were included. Patients were followed up for an average of 6.2 years (959.6 patient-years). Persistent LGD was defined as detection of LGD on ≥2 consecutive occasions during the follow-up period and extent as either unifocal (LGD at one level of BE segment) or multifocal (>1 level). Histology specimens were reviewed by 2 blinded pathologists. RESULTS: Six patients developed EAC (incidence of 0.44%/year), and 21 developed HGD (incidence of 1.6%/year). The incidence of the combination of HGD and EAC was 1.83%/year. There were no associations between presence of prevalent, incident, or persistent LGD and the extent of LGD with progression rates. Based on consensus diagnosis of 88 reviewed specimens, there was no difference in the progression of LGD to either EAC (the incidence based on analyses by the local pathologist was 0.18%/year, the incidence when there was agreement between the local and one central pathologist was 0.21%/year, and the incidence when all 3 pathologists were in agreement was 0.39%/year) or combined HGD and EAC (0.94%/year, 0.87%/year, and 0.84%/year, respectively). CONCLUSIONS: Overall, patients with BE and LGD have a low annual incidence of EAC, similar to nondysplastic BE. There are no risk factors for progression and there is significant interobserver variation in diagnosis, even among expert pathologists.

Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma.

The overall 5 year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: 1) an independent cohort of VLTS and 2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival.

Clinical significance of the duplicated muscularis mucosae in Barrett esophagus-related superficial adenocarcinoma.

OBJECTIVE: The purpose of this study was to evaluate the relationship between the depth of invasion within the mucosal compartment, with particular attention to the duplicated muscularis mucosae, and survival after esophagectomy performed as treatment for Barrett esophagus-related superficial adenocarcinoma. METHODS: A total of 185 patients with pT1 esophageal adenocarcinoma treated by esophagectomy without induction therapy were identified. Depth of invasion was subdivided into invasion into the lamina propria (LP), into the inner muscularis mucosae, between the inner and outer muscularis mucosae, and into the outer muscularis mucosae (OMM), with comparison with tumors invading the inner one third of the submucosa (SM-1). Patient and tumor characteristics were compared among the 5 groups using the χ test or the Kruskal-Wallis test. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The prognostic effect of depth of invasion on survival was assessed with Cox proportional hazards analysis. RESULTS: Depth of invasion was LP (n=68), inner muscularis mucosae (n=38), BMM (n=11), OMM (n=33), and SM-1 (n=35). There was no significant difference in sex or age among groups. One of 150 patients with intramucosal adenocarcinoma (0.7%; LP, pN2) and 3 of 35 patients with SM-1 (8.6%; all pN1) had nodal disease. There were no significant differences in survival among the groups. CONCLUSIONS: Depth of invasion relative to the duplicated muscularis mucosae for tumors restricted to the mucosal compartment does not affect survival in Barrett esophagus-related superficial adenocarcinoma. Patients with SM-1 tumor had survival similar to those patients with tumor invasion into the OMM.