Do pre-existing complications affect the failure to rescue quality measures?

BACKGROUND: A project sponsored by the University Health System Consortium has addressed the inaccuracy and high variability across institutions concerning the use of the failure to rescue (FTR) quality indicator defined by the Agency for Healthcare Research and Quality (AHRQ). Results indicated that of the complications identified by the quality indicator, 29.5% were pre-existing upon hospital admission. OBJECTIVE: The purpose of our study was to investigate the possible bias to FTR measures by including cases of complications that were pre-existing at admission. METHODS: Hospital discharges between 1 January 1996 and 30 September 2007 were retrospectively gathered from administrative databases. Using definitions outlined by the AHRQ and the National Quality Forum (NQF), FTR rates were calculated. Using present on admission coding, FTR rates were recalculated to differentiate between the rates of pre-existing and that of acquired cases. RESULTS: Using the AHRQ definition, the overall FTR rate was 11.60%. The FTR rate for patients with pre-existing complications was 8.85%, whereas patients with complications acquired during hospitalisation had an FTR rate of 18.46% (p<0.001). The NQF FTR rate was 9.93%. Pre-existing and acquired FTR rates using the NQF measure were 9.42% and 12.77%, respectively (p<0.001). CONCLUSIONS: Current definitions of FTR measures meant to identify inhospital complications appear biased by the inclusion of problems at admission. Furthermore, many patients with these complications are excluded from the algorithms. When taking into account the timing of the "complications", these measures can be useful for internal quality control. However, it should be stressed that the usefulness of the measures to compare institutions will be dependent on coding practices of institutions. Validation using chart review may be required.

Decreased expression of Fas (CD95/APO1) associated with goblet cell metaplasia in Barrett's esophagus.

Fas ligand (FasL) has been shown to induce apoptosis in cells expressing its receptor Fas. We have recently shown that Fas ligand is overexpressed in all cases of Barrett's metaplasia (BM) with dysplasia and esophageal adenocarcinomas, and in a few cases of BM negative with dysplasia. The aim of this work was to determine the status of Fas expression in BM with and without dysplasia or carcinoma. Formalin-fixed and paraffin-embedded tissue sections from esophageal biopsies and esophagectomy specimens with BM, with and without dysplasia and carcinoma, were immunostained for Fas and FasL using the immunoperoxidase technique. The percentage of positive cells in each case was evaluated and compared with the degree of dysplasia. When Fas expression was assessed in glands with goblet cell metaplasia, Fas immunoreactivity was either undetected or present in less than 10% of the cells in 85% of the cases, and only 1 (4%) of the 28 cases examined showed Fas immunoreactivity in more than 25% of the cells. When we compared Fas expression in goblet cell-containing glands with glands of gastric cardia phenotype, we found that in the 26 cases of BM with or without dysplasia Fas was completely undetectable in goblet cell-containing glands in 15 (58%) of the cases but was undetectable in only 3 (12%) of the glands with gastric cardia phenotype (P = .002). Fas is usually undetectable or is expressed at a low level in BM with or without dysplasia or carcinoma. Fas expression in goblet cell-containing glands is less frequent than in glands with gastric cardia phenotype in the same specimens. BM with dysplasia or carcinoma overexpress FasL, so decreased Fas expression may protect BM with dysplasia and carcinoma from self-destruction while allowing them to evade immune surveillance.

Fas ligand expression in esophageal carcinomas and their lymph node metastases.

BACKGROUND: Although esophageal adenocarcinomas (EADCA) have been shown to have substantially reduced or absent Fas expression, the status of Fas ligand (FasL) in these tumors, especially adenocarcinomas, is largely unknown. METHODS: Using immunohistochemistry, the authors investigated FasL expression in sections of formalin fixed, paraffin embedded tissue from 13 EADCA. They also studied sections of 15 esophageal squamous cell carcinomas (ESCCA) and of lymph node metastases from 7 EADCA and 4 ESCCA. The percentage of FasL positive cells in each tumor was recorded. FasL expression in EADCA was compared with that in ESCCA and with lymph node status. Statistical analysis was performed using the Fisher exact test. RESULTS: No specific staining pattern was seen in adenocarcinomas. In ESCCA, FasL was often located in the cells at the periphery of tumor nests. All (100%) of EADCA showed FasL expression in greater than 25% of the cancer cells, and all were associated with lymph node metastasis. Fifty-three percent of ESCCA showed FasL expression in greater than 25% of the cancer cells and 33% had lymph node metastasis. Expression of FasL in greater than 25% of tumor cells was associated with a significantly higher incidence of lymph node metastasis (P=0.0001). All lymph node metastases from esophageal carcinomas showed FasL immunoreactivity in greater than 50% of the metastatic tumor cells. CONCLUSIONS: FasL expression in greater than 25% of cancer cells correlates with a high incidence of lymph node metastasis in esophageal carcinomas. All cancer metastases in lymph nodes express FasL in >50% of the cells. These findings indicate that FasL plays an important role in the immune evasion and metastasis of esophageal carcinomas.

Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas.

Cancers cells utilize more glucose and amino acids than their benign counterparts. Overexpression of the facilitative glucose transporter Glut1 in human cancers was found to correlate with aggressive biologic behavior. The aim of this work was to determine whether the neutral amino acid transporter ASCT1 is expressed in human esophageal carcinomas, and to correlate the findings with Glut1 expression. Sections of formalin-fixed and paraffin-embedded tissue from 42 cases of esophageal carcinomas were entered in the study. Immunohistochemical staining was performed using a rabbit anti-ASCT1 IgG developed in our laboratory, and anti-Glut1 antibody, using standard avidin-streptavidine immunoperoxidase method. Sections of formalin-fixed and paraffin-embedded HepG2 cells were used as positive controls. The percent of ASCT1-positive cells was scored. Statistical analysis was performed using Fisher's exact test. ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous. Significantly more adenocarcinomas expressed ASCT1 than squamous cell carcinomas (p < 0.0001), whereas Glut1 expression was similar in both tumor types. There was no association between the expression of either transporter and lymph node metastasis. Glut1 was expressed more often in the better differentiated than the poorly differentiated squamous carcinomas (p = 0.003). These results suggest that unlike in squamous cell carcinoma, ASCT1 plays a significant role in the recruitment of amino acids in adenocarcinoma of the esophagus, and suggest that the metabolic needs, and uptake of nutrients, are regulated differently in these two tumor types. Additional studies with larger number of patients are needed to determine the biological significance of ASCT1 expression in esophageal carcinomas.

Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett's metaplasia of the esophagus.

Esophageal and colorectal adenocarcinomas overexpress Fas ligand (FasL), which can protect them from immune surveillance. The aim of this work was to determine whether FasL expression, and therefore FasL-dependent immune evasion, occurs early during malignant transformation in Barrett's metaplasia (BM) of the esophagus, and in the large intestine. Sections of formalin-fixed and paraffin-embedded tissue from esophageal and large bowel biopsies and resection specimens were immunostained for FasL using standard immunoperoxidase technique. The percentage of positive cells was correlated with the degree of dysplasia in BM and with the size and villous architecture of colorectal adenomas. In BM, FasL was detected in 55% of cases negative for dysplasia, and was associated with inflammation in almost all positive cases. By contrast, all cases of BM (100%) with low- or high-grade dysplasia were FasL-positive. In the large intestine, 25% of small adenomas were negative for FasL, and FasL overexpression was significantly more frequent in larger adenomas and in adenomas with tubulovillous or villous morphology. Our results suggest that (1) FasL overexpression is acquired early during malignant transformation of BM and the large bowel and (2) FasL overexpression occurs relatively earlier during malignant progression of BM than the large bowel, probably as a result of the preceding repeated inflammation.