The management and long-term outcomes of endoscopic and surgical treatment of early esophageal adenocarcinoma.

Endoscopic resection (ER) for early (pT1) esophageal adenocarcinoma can be justified if the rate of coexisting lymph node (LN) metastasis is less than the mortality rate from esophagectomy. This study examines endoscopic and surgical outcomes, histological assessment of submucosal (sm) disease, factors influencing LN metastasis, and the safety of treating pT1b disease endoscopically. Histopathological reexamination recorded thickness, width and depth of sm invasion, grade, presence of lymphovascular invasion (LVI), resection margin status and tumor stage. Multivariate analysis was employed to evaluate the factors influencing survival and LN metastasis. Rate of LN metastasis for pT1 low-risk (LR: sm invasion < 500 µm, G1-2, no LVI) or high-risk (HR: sm invasion >500 µm, G3-4 or LVI) disease were analyzed. Ninety three patients underwent ER and 96 underwent esophagectomy. We demonstrate conflicting histological methods of sm disease reporting, which may explain the difference in LN metastasis rate between reported surgical & endoscopic series. Multivariate analysis confirmed age, T stage, and presence of LN metastases were the independent factors predicting poor prognosis. Tumor thickness as well as grade, T stage, LVI were predictors of LN metastasis. Rates of LN metastasis are <2% in LR sm1 disease, and >15% in HR sm1 disease. Pathological reporting of sm invasion should be updated for uniform analysis of endoscopic and surgical specimens. Following rigorous histopathological examination and within a close endoscopic follow-up regimen, pT1a and pT1b LRsm1 disease may be treated with curative intent endoscopically, whereas pT1b HRsm1-sm3 disease should be offered surgery.

Phenotypic anchoring of arsenic and cadmium toxicity in three hepatic-related cell systems reveals compound- and cell-specific selective up-regulation of stress protein expression: implications for fingerprint profiling of cytotoxicity.

Exposure of cells to toxic chemicals is known to up-regulate the expression of a number of stress proteins (SPs), including metallothionein (MT) and members of the heat shock protein (HSP) family, and this response may allow the development of a fingerprint profile to identify mechanisms of toxicity in an in vitro toxicology setting. To test this hypothesis, three hepatic-derived cell culture systems (rat hepatoma FGC4 cell line, rat hepatocytes, human hepatoma HepG2 cell line) were exposed to cadmium (as CdCl2) and arsenic (as NaAsO2), two compounds believed to exert their toxicity through an oxidative stress mechanism, under conditions of phenotypic anchoring defined as minimal and mild toxicity (approximately 5 and 25% reduction in neutral red uptake, respectively). The expression of six SPs--MT, HSP25/27, HSP40, HSP60, HSP70, and HSP90--was then determined by ELISA. Expression of four of these SPs--MT, HSP25/27, HSP40 and HSP70--was up-regulated in at least one experimental condition. However, the patterns of expression of these four SPs varied across the experimental conditions, according to differences in toxicant concentration and/or level of toxicity, cell-type and toxicant itself. This lack of uniformity in response of a focussed set of mechanistically defensible targets suggests that similar problems may emerge when using more global approaches based on genomics and proteomics, in which problems of redundancy in targets and uncertain mechanistic relevance will be greater.