Comparison of prevalence and resection rates in patients with esophageal squamous cell carcinoma and adenocarcinoma

AbstractSince 1987 we have observed a predominance of adenocarcinoma in patients undergoing esophagectomy because of carcinoma at our institution. To discover whether this observation represented an actual change in the prevalence of adenocarcinoma, the Johns Hopkins Hospital pathology records were reviewed for the years 1959 to 1994. Overall, esophageal squamous cell carcinoma was the most common histologic type with 817 cases identified versus 284 cases of adenocarcinoma. The number of patients with squamous cell carcinoma rose slowly from 1959 to 1992 but since 1992 has decreased. Whereas adenocarcinoma was uncommon before 1978, its frequency has since increased markedly, exceeding that of squamous cell carcinoma in 1994. The number of patients with adenocarcinoma who underwent surgical resection has equaled or exceeded the number of those treated nonoperatively for all recorded years. Therefore the predominance of adenocarcinoma in patients undergoing esophageal resection for carcinoma appears to result from two factors: an overall increase in the prevalence of adenocarcinoma since 1978 and an increased likelihood of resection for patients with these tumors. (J Thorac Cardiovasc Surg 1996;112:130-6

Inhibition of SIRT1 Reactivates Silenced Cancer Genes without Loss of Promoter DNA Hypermethylation

The class III histone deactylase (HDAC), SIRT1, has cancer relevance because it regulates lifespan in multiple organisms, down-regulates p53 function through deacetylation, and is linked to polycomb gene silencing in Drosophila. However, it has not been reported to mediate heterochromatin formation or heritable silencing for endogenous mammalian genes. Herein, we show that SIRT1 localizes to promoters of several aberrantly silenced tumor suppressor genes (TSGs) in which 5′ CpG islands are densely hypermethylated, but not to these same promoters in cell lines in which the promoters are not hypermethylated and the genes are expressed. Heretofore, only type I and II HDACs, through deactylation of lysines 9 and 14 of histone H3 (H3-K9 and H3-K14, respectively), had been tied to the above TSG silencing. However, inhibition of these enzymes alone fails to re-activate the genes unless DNA methylation is first inhibited. In contrast, inhibition of SIRT1 by pharmacologic, dominant negative, and siRNA (small interfering RNA)–mediated inhibition in breast and colon cancer cells causes increased H4-K16 and H3-K9 acetylation at endogenous promoters and gene re-expression despite full retention of promoter DNA hypermethylation. Furthermore, SIRT1 inhibition affects key phenotypic aspects of cancer cells. We thus have identified a new component of epigenetic TSG silencing that may potentially link some epigenetic changes associated with aging with those found in cancer, and provide new directions for therapeutically targeting these important genes for re-expression

Anesthesia advanced circulatory life support

The constellation of advanced cardiac life support (ACLS) events, such as gas embolism, local anesthetic overdose, and spinal bradycardia, in the perioperative setting differs from events in the pre-hospital arena. As a result, modification of traditional ACLS protocols allows for more specific etiology-based resuscitation. Perioperative arrests are both uncommon and heterogeneous and have not been described or studied to the same extent as cardiac arrest in the community. These crises are usually witnessed, frequently anticipated, and involve a rescuer physician with knowledge of the patient's comorbidities and coexisting anesthetic or surgically related pathophysiology. When the health care provider identifies the probable cause of arrest, the practitioner has the ability to initiate medical management rapidly. Recommendations for management must be predicated on expert opinion and physiological understanding rather than on the standards currently being used in the generation of ACLS protocols in the community. Adapting ACLS algorithms and considering the differential diagnoses of these perioperative events may prevent cardiac arrest

A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus

National Cancer Institute grants U01 CA152926 (CISNET) (to EGL, JJ, and WDH) and U01 CA182940 (BG-U01) (to EGL and WDH). National Science Foundation (www.nsf.gov) under grant no. DGE-0718124 (to KC

Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma

Purpose: This randomized phase II, parallel-design study evaluated preoperative combined modality therapy and the matrix metalloprotease (MMP) inhibitor prinomastat in patients with resectable adenocarcinoma of the esophagus that were stage II or greater. The objectives of the trial were to determine pathologic complete response rate (pCR), overall response rate, progression-free survival, pattern of disease relapse, and two-year and overall Survival. Patients and Methods: Preoperative staging included computed tomography, endoscopic ultrasound, and, when feasible, laparoscopy. Eligible patients were randomized to preoperative prinomastat or placebo. plus continuous infusion 5-FU, cisplatin, paclitaxel, and Concurrent radiotherapy. Esophagectomy was performed on day 71. Adjuvant paclitaxel and prinomastat were available to all Study patients. Results: Between August 2000 and June 2001, 15 of a planned 78 patients were randomized into the trial. One patient after randomization withdrew consent. Fourteen patients, 7 in each arm. completed preoperative treatment and Surgery. pCR was achieved in 5 patients: 1/7 prinomastat and Q 7 placebo. Disease improvement was achieved in 7 patients; 5/7 prinomastat and 2/7 placebo. At a median follow-up of 28 months, 7 patients (2 prinomastat, 5 placebo) are alive with no evidence of disease. The primary prinomastat related toxicity was moderate to severe musculoskeletal toxicity interfering with daily function. This toxicity was managed with treatment rest, dose reduction, or discontinuation. Five patients (3 prinomastat and 2 placebo) had life-threatening thrombo-embolic events, which led to early evaluation of safety and efficacy, and subsequent termination of the Study. Conclusion: All patients, regardless of treatment arm, were able to successfully undergo neoadjuvant combined modality therapy and esophagectomy. However, early closure of the study due to unexpected thrombo-embolic events precluded any conclusions regarding clinical activity of prinomastat in locally advanced esophageal cancer patients