Validation of the Rockall risk scoring system in upper gastrointestinal bleeding.
BACKGROUND: Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study. AIMS: To assess internal and external validity of a simple risk scoring system recently developed by Rockall and coworkers. METHODS: Calibration and discrimination were assessed as measures of validity of the scoring system. Internal validity was assessed using an independent, but similar patient sample studied by Rockall and coworkers, after developing the scoring system (Rockall's validation sample). External validity was assessed using patients admitted to several hospitals in Amsterdam (Vreeburg's validation sample). Calibration was evaluated by a chi2 goodness of fit test, and discrimination was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Calibration indicated a poor fit in both validation samples for the prediction of rebleeding (p<0.0001, Vreeburg; p=0.007, Rockall), but a better fit for the prediction of mortality in both validation samples (p=0.2, Vreeburg; p=0.3, Rockall). The areas under the ROC curves were rather low in both validation samples for the prediction of rebleeding (0.61, Vreeburg; 0.70, Rockall), but higher for the prediction of mortality (0.73, Vreeburg; 0.81, Rockall). CONCLUSIONS: The risk scoring system developed by Rockall and coworkers is a clinically useful scoring system for stratifying patients with acute UGIB into high and low risk categories for mortality. For the prediction of rebleeding, however, the performance of this scoring system was unsatisfactory. (+info
Predicting delayed anxiety and depression in patients with gastrointestinal cancer.
The aim of this study was to examine the possibility of predicting anxiety and depression 6 months after a cancer diagnosis on the basis of measures of anxiety, depression, coping and subjective distress associated with the diagnosis and to explore the possibility of identifying individual patients with high levels of delayed anxiety and depression associated with the diagnosis. A consecutive series of 159 patients with gastrointestinal cancer were interviewed in connection with the diagnosis, 3 months (non-cured patients only) and 6 months later. The interviews utilized structured questionnaires assessing anxiety and depression [Hospital Anxiety and Depression (HAD) scale], coping [Mental Adjustment to Cancer (MAC) scale] and subjective distress [Impact of Event (IES) scale]. Patient anxiety and depression close to the diagnosis were found to explain approximately 35% of the variance in anxiety and depression that was found 6 months later. The addition of coping and subjective distress measures did little to improve that prediction. A model using (standardized) cut-off scores of moderate to high anxiety, depression (HAD) and intrusive thoughts (IES subscale) close to the diagnosis to identify patients at risk for delayed anxiety and depression achieved a sensitivity of 75% and a specificity of 98%. Levels of anxiety and depression at diagnosis predicted a similar status 6 months later. The results also indicated that the HAD scale in combination with the IES intrusion subscale may be used as a tool for detecting patients at risk of delayed anxiety and depression. (+info
Immunocytochemically detected free peritoneal tumour cells (FPTC) are a strong prognostic factor in gastric carcinoma.
We prospectively investigated the prognostic significance of free peritoneal tumour cells (FPTC) in a series of 118 patients with completely resected gastric carcinoma. Immunocytochemistry with the monoclonal antibody Ber-Ep4 was performed on cytospins from intraoperative peritoneal lavage specimens. Twenty-three patients (20%) had FPTC which was significantly correlated with pT and pN categories, stage, tumour size, lymphatic invasion, Lauren and WHO classifications and perigastric adipose tissue metastases. The median survival time for all FPTC positive compared with negative patients was significantly shorter (11 compared with >72 months), with estimated 5-year survival rates of 8% vs. 60%. None of the patients with FPTC had an early gastric cancer. In advanced tumour subgroups without and with serosal invasion (n = 59 and 35), there were 19% and 34% with FPTC. Multivariate survival analysis showed nodal status, FPTC, mesenteric lymphangiosis, and lymph node metastasis to the compartment III to be independent prognostic factors with relative risks of 6.6, 4.5, 2.9 and 2.2 respectively. Recurrent disease occurred in 91% of FPTC-positive and in 38% of FPTC-negative patients. FPTC had a positive predictive value of 91% and a specificity of 97% for tumour recurrence. FPTC is a strong negative, independent prognostic indicator for survival in gastric carcinoma. (+info
Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients.
Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of the widely used antineoplastic agent 5-fluorouracil (5FU), thereby limiting the efficacy of the therapy. To identify patients suffering from a complete or partial DPD deficiency, the activity of DPD is usually determined in peripheral blood mononuclear cells (PBM cells). In this study, we demonstrated that the highest activity of DPD was found in monocytes followed by that of lymphocytes, granulocytes and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in PBM cells proved to be intermediate compared with the DPD activity observed in monocytes and lymphocytes. The mean percentage of monocytes in the PBM cells obtained from cancer patients proved to be significantly higher than that observed in PBM cells obtained from healthy volunteers. Moreover, a profound positive correlation was observed between the DPD activity of PBM cells and the percentage of monocytes, thus introducing a large inter- and intrapatient variability in the activity of DPD and hindering the detection of patients with a partial DPD deficiency. (+info
Prognostic value of myocardial perfusion imaging in patients with high exercise tolerance.
BACKGROUND: Although high exercise tolerance is associated with an excellent prognosis, the significance of abnormal myocardial perfusion imaging (MPI) in patients with high exercise tolerance has not been established. This study retrospectively compares the utility of MPI and exercise ECG (EECG) in these patients. METHODS AND RESULTS: Of 388 consecutive patients who underwent exercise MPI and reached at least Bruce stage IV, 157 (40.5%) had abnormal results and 231 (59.5%) had normal results. Follow-up was performed at 18+/-2.7 months. Adverse events, including revascularization, myocardial infarction, and cardiac death, occurred in 40 patients. Nineteen patients had revascularization related to the MPI results or the patient's condition at the time of MPI and were not included in further analysis. Seventeen patients (12.2%) with abnormal MPI and 4 (1.7%) with normal MPI had adverse cardiac events (P<0.001). Cox proportional-hazards regression analysis showed that MPI was an excellent predictor of cardiac events (global chi2=13.2; P<0.001; relative risk=8; 95% CI=3 to 23) but EECG had no predictive power (global chi2=0.05; P=0.8; relative risk=1; 95% CI=0.4 to 3.0). The addition of Duke's treadmill score risk categories did not improve the predictive power of EECG (global chi2=0.17). The predictive power of the combination of EECG (including Duke score categories) and MPI was no better than that of MPI alone (global chi2=13.5). CONCLUSIONS: Unlike EECG, MPI is an excellent prognostic indicator for adverse cardiac events in patients with known or suspected CAD and high exercise tolerance. (+info
Usefulness of fractional flow reserve to predict clinical outcome after balloon angioplasty.
BACKGROUND: After regular coronary balloon angioplasty, it would be helpful to identify those patients who have a low cardiac event rate. Coronary angiography alone is not sensitive enough for that purpose, but it has been suggested that the combination of optimal angiographic and optimal functional results indicates a low restenosis chance. Pressure-derived myocardial fractional flow reserve (FFR) is an index of the functional severity of the residual epicardial lesion and could be useful for that purpose. METHODS AND RESULTS: In 60 consecutive patients with single-vessel disease, balloon angioplasty was performed by use of a pressure instead of a regular guide wire. Both quantitative coronary angiography (QCA) and measurement of FFR were performed 15 minutes after the procedure. A successful angioplasty result, defined as a residual diameter stenosis (DS) <50%, was achieved in 58 patients. In these patients, DS and FFR, measured 15 minutes after PTCA, were analyzed in relation to clinical outcome. In those 26 patients with both optimal angiographic (residual DS by QCA /=0.90) results, event-free survival rates at 6, 12, and 24 months were 92+/-5%, 92+/-5%, and 88+/-6%, respectively, versus 72+/-8%, 69+/-8%, and 59+/-9%, respectively, in the remaining 32 patients in whom the angiographic or functional result or both were suboptimal (P=0.047, P=0.028, and P=0.014, respectively). CONCLUSIONS: In patients with a residual DS /=0.90, clinical outcome up to 2 years is excellent. Therefore, there is a complementary value of coronary angiography and coronary pressure measurement in the evaluation of PTCA result. (+info
The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.
At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy. (+info
Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer.
BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis. METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size. RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold. CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy. (+info