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Treatment and prognostic factors in patients with hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma is a leading cause of death from cancer worldwide. Survival of patients depends on tumor extension and liver function, but yet there is no consensual prognostic model. AIMS: To evaluate the influence on survival of pretreatment parameters (clinico-laboratorial, liver function, tumor extension, Okuda and Cancer of the Liver Italian program (CLIP) staging) and treatment modalities. METHODS: We retrospectively analyzed 207 patients, diagnosed between 1993 and 2003. The initial treatment was: surgery--six patients; radiofrequency ablation--21; percutaneous ethanol injection--29; transarterial chemoembolization--49; tamoxifen--49; supportive care alone--53. Factors determining survival were assessed by Kaplan-Meier method and Cox regression models. RESULTS: Median survival was 24 months. In univariate analysis, Child-Pugh classification and Model for end-stage liver disease (MELD) score, portal vein thrombosis (PVT), tumor size, number of lesions, Okuda and CLIP scores were all associated with prognosis (P < 0.001). Alpha-fetoprotein levels were not predictive of survival. Independent predictors of survival were ascites, bilirubin, PVT and therapeutic modalities (P < 0.001). In early stage hepatocellular carcinoma (HCC), survival was similar for both percutaneous ablation modalities, either radiofrequency or ethanol injection (P = NS). In advanced HCC, survival was better in patients receiving tamoxifen than supportive care alone (P < 0.001). CONCLUSION: This study reinforces the importance of baseline liver function (Child-Pugh classification and MELD score) in the survival of patients with HCC, although staging systems allowed the stratification of patients in different prognostic groups. Ascites, bilirubin and PVT were independent pretreatment predictors of survival. All treatments influenced the patient's outcome, whether in early or advanced stages.

Adult↗

Why does C-reactive protein increase in non-ST elevation acute coronary syndromes? Role of myocardial damage.

INTRODUCTION: C-reactive protein is an important prognostic indicator for early risk stratification in patients with an acute coronary syndrome. The mechanisms underlying the elevation of C-reactive protein in these patients have not been fully understood. We studied the factors related to the increase of this acute-phase reactant. METHODS AND RESULTS: Within a single-centre registry, 419 consecutive patients admitted for a non-ST elevation acute coronary syndrome were studied. Serum high sensitivity C-reactive protein was measured late (median 3 days) after admission. Clinical, electrocardiographic, biochemical and angiographic variables were recorded. In the multivariate analysis, an increased C-reactive protein (n=162) was related to high levels of troponin I (OR 2.5 (1.6-4) P<0.001) and to a Killip class>1 at presentation (OR 2.9 (1.6-5.4) P<0.001). The coronary angiographic characteristics were not related to C-reactive protein. Finally, in 52 patients with no previous heart disease in whom regional dysfunction was quantified by left ventriculography the presence of a significant (>6 chords) regional dysfunction was significantly related to C-reactive protein (OR 5.1 (1.7-15.3) P=0.006) CONCLUSION: Our results indicate that in acute coronary syndromes elevated levels of C-reactive protein late after admission are mainly related to clinical, biochemical and angiographic evidences of myocardial damage. The prognostic utility of this parameter could be in part explained by its relationship with a major regional dysfunction.

Acute Disease↗

Wall motion score index and ejection fraction for risk stratification after acute myocardial infarction.

BACKGROUND: The prognostic importance of regional systolic function, as assessed by wall motion score index (WMSI), compared with global function, as assessed by left ventricular ejection fraction (LVEF), has not been assessed in large populations after acute myocardial infarction. METHODS: Echocardiograms, including the assessment of WMSI and LVEF, were performed in 767 patients with acute myocardial infarction at a median of 1 day (25th and 75th percentiles 0-2 days) after admission. Patients were followed for a median of 19 months (range 12-28 months). Cox proportional hazards models were constructed for the primary study end point (all-cause mortality) and for a secondary end point (hospitalization for congestive heart failure). RESULTS: During follow-up (median 40 months; range 32-50 months), 216 patients died and 54 patients were hospitalized for congestive heart failure. By univariate analysis, both LVEF (P < .0001) and WMSI (P < .0001) were powerful predictors of all-cause mortality. By a forward conditional Cox model, WMSI proved to be an independent predictor of death (hazard ratio 1.15 per 0.2-unit increase, 95% CI 1.10-1.21, P < .0001). When WMSI was included in the model, LVEF did not provide additional prognostic information (P = .77). Wall motion score index also proved to be an independent predictor of hospitalization for congestive heart failure (hazard ratio 1.21 per 0.2-unit increase, 95% CI 1.07-1.37, P = .002), whereas LVEF did not (P = .56). CONCLUSION: Both LVEF and WMSI provide powerful prognostic information after acute myocardial infarction; however, the predictive power of WMSI is greater.

Aged↗

Combined stratification of refractory anemia according to both WHO and IPSS criteria has a prognostic impact and improves identification of patients who may benefit from stem cell transplantation.

A retrospective analysis of the relationship between the initial classification according to either FAB or WHO criteria, the presence of risk factors and the type of therapy including stem cell transplantation (SCT) on the survival was performed in a group of 106 patients with primary myelodysplastic syndrome (MDS) of FAB RA subtype. Allogeneic SCT early in the course of the disease did not significantly affect median survival in RA patients evaluated either according to FAB criteria (63.2 months in 17 SCT patients versus 64.4 months in 89 non-transplanted (non-SCT) patients) or in subgroups classified separately according to WHO (64.0 months in SCT versus 91.0 months in non-SCT RA patients and 66.2 months in SCT versus 43.0 months in non-SCT refractory cytopenia with multilineage dysplasia (RCMD) patients) or International Prognostic Scoring System (IPSS) criteria despite decreased incidence of leukemic transformation (5% in SCT versus 32% in non-SCT patients). Neither univariate or multivariate analysis of different clinical and laboratory parameters revealed a significant effect of SCT on 3 or 5 years survival in RA patients. The most probable explanation was a relatively high rate of transplantation related mortality (41%) on one hand together with a slow disease progression towards leukemia (24% at 5 years in non-SCT) on the other hand. A more refined stratification of patients based on the combined WHO morphology classification and IPSS cytogenetic criteria revealed subgroup of 11 non-SCT patients with RCMD and poor karyotype with median survival significantly different from that in five SCT patients (9.2 months in non-SCT versus 89.3 months in SCT, P=0.05). Thus, combined WHO morphology/IPSS cytogenetics criteria may be helpful for identification of the high risk patients with the RA group who may benefit from early SCT despite the relatively high incidence of SCT-related complications.

Anemia, Refractory↗

Prognostic use of human leukocyte antigen genotyping for rheumatoid arthritis susceptibility, disease course, and clinical stratification.

HLA markers of the class II region are important for determination of the predisposition to RA, clinical manifestations, and rate of progression of joint destruction in this autoimmune disease. Furthermore, evidence emerges indicating that HLA markers also have an impact on treatment outcome in RA. Currently, several immunopathogenetic models of HLA-dependent influences in RA are under debate. These models insufficiently explain the graded influence of HLA-DR and HLA-DQ on manifestation and joint destruction, however. Currently, there is not enough evidence to unequivocally identify a primary susceptibility locus or to pinpoint the HLA-dependent mechanism in RA. Overall, the influence of HLA class II markers on disease susceptibility is rather restricted, and, in turn, their utility in establishing the diagnosis of RA is of limited use. Although relative risks are higher for the association of particular genotypes with extra-articular forms of RA, HLA genotyping may not contribute to prognostication in individual patients but may aid in disease stratification. In contrast, HLA genotyping in early RA, particularly when combined with the determination of RFs and determination of the presence of bony erosions, is of value to identify patients at risk for poor outcome. In turn, these patients may benefit from early aggressive therapy, and HLA genotyping should be useful to aid in risk stratification in patients and thus helpful for the choice of treatment. Lastly, disease and risk stratification based on HLA markers along with the elucidation of HLA-dependent mechanisms may facilitate the development of specific immunotherapy modalities.

Arthritis, Rheumatoid↗

[Role of the assay of serum beta 2 microglobulin in the clinical evaluation of myeloma].

The survival of individual patients with multiple myeloma ranging from a few weeks to several years, careful pretreatment evaluation of prognostic factors is extremely important. Several methods of stratification are available, but in spite of their validity they present a number of problems, particularly with regard to their inter-reproducibility. In addition, they are of no help to evaluate response to chemotherapy, quality of remission, plateau phase or kinetics of relapse. Recent studies have clearly demonstrated that serum beta-2 microglobulin, as a single variable, is the best individual determinant as a prognostic marker in multiple myeloma. Using this assay and serum albumin as prognostic determinants, a simple stratification, superior to the three previously available methods, was developed. Serum beta-2 microglobulin is a very useful marker in the follow-up of most multiple myeloma patients. It appears to be a key measurement for assessing the prognosis and response to treatment of these patients.

Humans↗

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Adolescent↗

Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden.

BACKGROUND: Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST. METHODS: All patients (n=1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3-1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk-group stratifications, were analyzed statistically. RESULTS: Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty-four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor-related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor-related deaths occurred in only 2 of 170 of patients (1.2%) with very-low-risk, low-risk, or intermediate-risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high-risk group and the overtly malignant group). CONCLUSIONS: GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk-group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index.

Age Factors↗

Quantitative histopathology in lymph node-negative breast cancer. Prognostic significance of mitotic counts.

Reliable prognostic factors are needed to improve the stratification of patients with lymph node-negative breast cancer to different therapy modalities. We investigated the prognostic value of quantitative histopathology in a retrospective study of 98 "low-risk" breast cancer patients (T1+2N0M0) with a median follow-up of 9 years. An interactive video system and stereological and morphometric techniques were used to obtain estimates of four nuclear features (mean volume, mean profile area, volume fraction, and profile density), and two mitotic counts [mitotic profile frequency (MF) and mitotic profile density (MD)]. All measurements were performed in fields of vision sampled systematically from the whole tumour area of a routine histological section. Histological grade, histological type, and oestrogen receptor (ER) status was reassessed, whereas tumour diameter and age at diagnosis were recorded from the files. We found that all quantitative histopathological variables and ER status were correlated with histological grade. Single-factor prognostic analyses showed a highly significant value of MF (2p = 0.001) and a marginally significant value of MD (2p = 0.09), whereas no other variable approached statistical significance (2p > or = 0.25). In a multivariate Cox analysis, MF was the only parameter of significant independent prognostic value (2p = 0.03). Thus, the prognostic value of nuclear features found in previous studies could not be reproduced, whereas the marked value of mitotic counts for prediction of the outcome in patients with breast cancer was confirmed. Mitotic counts are easily obtained and may be of clinical value for identification of high-risk cases among patients with lymph node-negative breast cancer.

Adult↗

Prognostic factors in breast cancer: the value of the Nottingham Prognostic Index for patients treated in a single institution.

PURPOSE: The Nottingham Prognostic Index (NPI) is used to predict survival in patients with breast cancer. This index is based on tumor size, lymph node stage, and histological grade and allows the stratification of patients into three different prognostic groups. Our aim was to verify the effect of some prognostic variables on survival and to establish the independent influence of each of these variables by a survival regression analysis. We applied the NPI to the same group of patients to assess its predictive power and reproducibility. METHODS: We evaluated 311 women with breast cancer treated between January 1993 and December 1998. RESULTS: In a multivariate analysis (Cox proportional hazard model), only size, lymph node involvement, and histological grade were independent prognostic factors. The survival curves obtained after applying the NPI were similar to those for the factors with independent prognostic significance derived from our multivariate analysis. CONCLUSION: The NPI allows us to accurately predict prognosis, and we advocate its standardized use.

Adult↗

Incremental prognostic value of stress echocardiography over clinical and stress electrocardiographic variables in patients with prior myocardial infarction: "warranty time" of a normal stress echocardiogram.

BACKGROUND: Patients with prior myocardial infarction (MI) are at increased risk of subsequent cardiac events (MI or cardiac death). The incremental prognostic value and warranty time of a normal stress echocardiogram in this high-risk population is not well defined. METHODS: We evaluated 251 consecutive patients (62 +/- 11 years; 64% males) with remote history of MI (>6 weeks) undergoing stress echocardiography (83% dobutamine). Ischemia was defined as a new reversible wall motion abnormality and/or biphasic response. Follow-up for up to 4 years (mean 2.9 +/- 1.0 years) for confirmed MI (n = 7) and cardiac death (n = 15) were obtained. RESULTS: Stress echocardiography effectively risk stratified patients into normal versus abnormal subgroups (Event rate 0.8% per year vs 4.2% per year; P = 0.01; RR = 5.6, 95% CI = 1.3-24.7). In patients with a normal stress echocardiogram, the event rate at the end of 6, 12, and 18 months were <1% per year. After 18 months the event rate in patients with a normal stress echocardiogram increased greatly (>1% per year). Stress echocardiography yields incremental prognostic value over clinical and stress electrocardiographic variables (Global chi-square increased from 12.4 to 25 to 31.1, P < 0.0001 both groups). CONCLUSIONS: Stress echocardiography yields appropriate risk stratification and prognosis and provides incremental prognostic value over clinical and stress electrocardiographic variables even in patients with prior MI. A normal stress echocardiogram portends a benign prognosis (<1% event rate/year) for up to 18 months.

Cardiotonic Agents↗

Pathology of nasopharyngeal carcinoma. Proposal of a new histologic classification correlated with prognosis.

To establish a new histologic classification with better correlation with patient prognosis, the histologic features of nasopharyngeal carcinoma (NPC) were correlated with prognosis and clinical stage among 494 patients who had been followed a minimum of 5 years after initial radiotherapy. A slight modification of World Health Organization (WHO) classification by the separation of spindle cell variant from the nonkeratinizing (NK) and undifferentiated carcinomas (UD) provided a better prognostic correlation: keratinizing squamous cell carcinoma (KS), spindle cell carcinoma (SP), round cell carcinoma (RC), and mixed cell carcinoma (Mix, or NK); 5-year survival rates were 21%, 41%, 51.8%, and 54%, respectively. This prognostic distinction was further improved by dividing the three nonkeratinizing carcinomas (SP, RC, and Mix) into two subtypes each, according to the degree of cell anaplasia and pleomorphism: Type A (with marked anaplasia and/or pleomorphism), and Type B (with moderate or little anaplasia). The three Type A carcinomas had very similar 5-year survival rates (33.3 to 38.6%), as did the three Type B carcinomas (60% to 71.8%). Therefore, a working formulation for the malignancy of NPC emerged: high-grade malignancy (KS; 5-year survival, 21%), intermediate malignancy (Type A carcinomas, 5-year survival, 30%-40%), and low-grade malignancy (Type B carcinomas, 5-year survival rate, 60%-72%). The prognostic distinction remained true after stratification by clinical stage. Therefore, the histologic condition of the tumor of NPC correlated with patient's prognosis.

Adolescent↗

Lessons from epidemiologic studies in clinical trials of traumatic brain injury.

Lessions from epidemiological studies. The Clinical Trial Group for Neurosurgery of the University of California San Diego (UCSD) is involved in epidemiological studies and trials of new pharmacological agents in traumatic brain injury. A great number (> 10,000) of patients has been prospectively analyzed forming an integrated database for further purposes. The development of these databases is based on earlier work by the European Neurosurgeons Jennett and Braakmann and the US-Traumatic Coma Data Bank Study. These studies allowed for the development of sophisticated data collection instruments which were used in the international Tirilizad Trials which enrolled over 1,100 patients. A major observation from that trial was that pretreatment hypotension or hypoxia could be unbalanced even in a large two arm blinded study. Another issue of the tirilazad trial was the influence of gender affecting not only outcome but also drug metabolism. Similar experiences were gathered with the phase-III trial on the competitive NMDA-receptor antagonist selfotel, which interferes with the excitotoxic amino acid glutamate as mediator of secondary brain damage, as ischemia-induced neuronal degeneration. Unfortunately, the trial, already underway, had to be prematurely aborted, since concurrent stroke studies with enrollment of nonintubated patients on low-dose selfotel revealed an increased number of deaths and other adverse events. A retrospective analysis did not confirm that Selfotel was associated with an increased mortality in TBI, but there was also no evidence that the drug was efficacious. A problem here was that a major portion of patients did not have intracranial mass lesions (contusion, subdural haematoma) on CT, questioning whether these had a treatment responsive brain injury. Both studies on tirilazad or selfotel underscore the significance of well designed and conducted phase-I and -II trials to characterize the pharmacokinetics of the agent, to confirm availability of drug in the brain, and to identify a sufficient number of patients with lesions responding to the drug. A major issue is the blood-brain barrier permeability of the agent under study. Further, the phenomenon of secondary deterioration - neurological worsening - turned out as a powerful predictor of poor outcome. The findings and conclusions of both clinical trials (tirilazad, selfotel) were utilized for a subsequent patient study on CP101-606 in consultation with the Pfizer company, the US Brain Injury Consortium, and the San Diego Clinical Trial Group. The patient population was a priori selected towards responsiveness of the brain lesions to the treatment. The major conclusions are: I Development of therapeutic regimens targeted towards the mechanisms of brain injury. II Availability of adequate preclinical data. III Directing treatment towards an appropriate patient population. IV Central gathering and interpretation of the neuroradiological findings. V Monitoring of trial center performance. VI Stratification and pre-trial prognostic analysis for identification of subgroups.

Brain Injuries↗

Detection of lymph node micrometastases and isolated tumor cells in sentinel and nonsentinel lymph nodes of colon cancer patients.

About 20% to 30% of colon cancer patients classified as node negative by routine hematoxylin-eosin (H&E) staining are found to have micrometastases (MM) or isolated tumor cells (ITC) in sentinel lymph nodes (SLNs) if analyzed by step sections and immunohistochemistry (IHC). Whether SLNs are in this respect representative for all lymph nodes was addressed in this study. SLNs were identified using the intraoperative blue dye detection technique. If all lymph nodes (SLNs and non-SLNs) of a patient were negative by routine H&E staining, they were step-sectioned and analyzed by IHC using pancytokeratin antibodies. We identified at least one SLN in 47 of the 55 patients (85%) and examined a median of 26 lymph nodes per patient (range 10-59). By routine H&E staining, 14 of the 47 patients showed lymph node metastases (30%); the remaining 33 were classified as node-negative. In this group (33 patients), 1011 lymph nodes were analyzed by step sections and IHC: 14 of 70 SLNs. (20%) but only 37 of 941 non-SLNs (4%) had MM/ITC (p < 0.001). Furthermore, 13 of the 33 H&E-negative patients were found to have MM/ITC (39%). In 11 of the 13 patients, MM/ITC were identified in both SLNs and non-SLNs in 1 patient in the SLN only, and in 1 patient in a non-SLN only (sensitivity for the identification of MM/ITC: 92%; negative predictive value: 95%). The SLN biopsy is a valid tool to detect, as well as exclude, the presence of MM/ITC in colon cancer patients. Our results may be of prognostic relevance and influence patient stratification for adjuvant therapy trials.

Aged↗

Preoperative clinical assessment and dipyridamole thallium-201 scintigraphy for prediction and prevention of cardiac events in patients having major noncardiovascular surgery and known or suspected coronary artery disease.

The aim of this study was to assess the relative prognostic use of clinical risk stratification and intravenous dipyridamole thallium-201 scintigraphy in patients with an intermediate to high prevalence of coronary artery disease (CAD) who have undergone major noncardiovascular surgery, and to assess the effects of medical therapy or coronary revascularization based on the result of this clinical scintigraphic screening on perioperative cardiac morbidity and mortality. Patients (n = 161) with an intermediate to high likelihood of CAD had clinical assessment and intravenous dipyridamole planar thallium-201 testing which was analyzed semiquantitatively. Cardiac events were cardiac death (n = 9), nonfatal myocardial infarction (n = 6), acute pulmonary edema (n = 6), and unstable angina (n = 4). Multiple (> or = 2) clinical risk variables predicted any cardiac event (p = 0.04). Presence of multiple (> or = 2) abnormal thallium-201 segments was the only independent predictor of cardiac death or nonfatal myocardial infarction (p < 0.001), and was the most powerful multivariate predictor of any cardiac event (p < 0.002). Patients with an abnormal dipyridamole thallium-201 scan had a higher risk of perioperative cardiac death, myocardial infarction (18% vs 2%; p < 0.001), or any perioperative cardiac event (27% vs 6%; p < 0.001) when compared with those with a normal scan. Preoperative changes in anti-ischemic therapy or coronary revascularization in 36 of 72 patients with abnormal dipyridamole thallium-201 studies reduced perioperative death or myocardial infarction from 31% to 6% (p < 0.01), and all cardiac events from 47% to 8% (p < 0.001) compared with those in patients without intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Chi-Square Distribution↗

TGF-beta1, TNF-alpha and cytochrome c in human astrocytic tumors: a short-term follow up and correlation with survival.

OBJECTIVES: To evaluate the association of signals of apoptosis namely, TGF-beta1, TNF-alpha and cytochrome c release in cytoplasm with survival rate to determine the potential use of such parameters as predictive markers for patients with astrocytomas. DESIGN AND METHODS: We measured TGF-beta1, TNF-alpha and cytoplasmic cytochrome c in 30 astrocytic tumors Grade II, III and IV. RESULTS: We found that TNF-alpha and cytochrome c release in Grade IV tends to be significantly lower than those in Grade II, whereas TGF-beta1 did not significantly change in the different grades. Patients with astrocytic tumors having elevated cytochrome c showed a better survival rate compared to those with less release. There is neither a correlation shown between TNF-alpha and cytochrome c release nor between TNF-alpha and patient survival. TGF-beta1 was positively correlated with cytochrome c release. Patients showing such correlation had increased survival rate over 18 months follow up period. CONCLUSION: These data suggest that TGF-beta1 and cytochrome c may be useful prognostic markers that help patients' stratification and in adjusting the disciplines of therapy.

Adolescent↗

Prognostic value of stress Tc-99m tetrofosmin SPECT in patients with previous myocardial infarction: impact of scintigraphic extent of coronary artery disease.

BACKGROUND: Our objective was to assess the prognostic value of the scintigraphic extent of coronary artery disease on stress technetium 99m tetrofosmin single photon emission computed tomography in patients with previous myocardial infarction. METHODS AND RESULTS: We studied 383 patients (280 men and 103 women; mean age, 60 +/- 11 years) more than 3 months after an acute myocardial infarction by exercise bicycle or dobutamine (up to 40 mug . kg -1 . min -1 ) stress Tc-99m tetrofosmin myocardial perfusion tomography. Stress images were acquired 1 hour after stress, and rest images were acquired 24 hours after stress testing. An abnormal study was defined as one demonstrating a reversible or fixed perfusion abnormality. Myocardial segments were assigned to corresponding coronary arteries as follows: the apex, anterior wall, and anterior septum were assigned to the left anterior descending coronary artery; the posterolateral wall was assigned to the left circumflex artery; and the basal posterior septum and inferior wall were assigned to the right coronary artery. During a mean follow-up of 4.3 +/- 2.1 years, 48 cardiac events occurred (36 cardiac deaths and 12 nonfatal myocardial infarctions). Myocardial perfusion was normal in 51 patients, abnormal in a single-vessel distribution in 170 patients, and abnormal in a multivessel distribution in 162 patients. The annual cardiac event rates in these groups were 0.4%, 2.6%, and 4%, respectively. In a multivariate analysis model, independent predictors of cardiac events were diabetes mellitus (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-4.5), history of congestive heart failure (OR, 2.7; 95% CI, 1.4-4), age (OR, 1.05; 95% CI, 1.01-1.08), and scintigraphic extent of coronary artery disease (OR, 4.2; 95% CI, 1.8-9.1). CONCLUSION: Stress Tc-99m tetrofosmin myocardial perfusion imaging provides independent prognostic information for the risk stratification of patients with previous myocardial infarction. The event rate is directly related to the scintigraphic extent of coronary artery disease. Patients with normal perfusion have an excellent event-free survival rate.

Coronary Artery Disease↗

Prognostic significance of allelic lost at chromosome 18q21 for stage II colorectal cancer.

BACKGROUND & AIMS: Allelic loss of a portion of chromosome 18q and lack of expression of deleted in colorectal cancer (DCC) protein has been reported as an adverse prognostic indicator for stage II (i.e., Dukes' B2) colorectal cancer. Our aim was to assess whether the DCC gene locus was responsible. METHODS: We amplified five DNA microsatellite markers located on chromosome 18q21 surrounding or within the DCC gene locus, including a DCC intragenic (TA)n microsatellite, from DNA microdissected and isolated from paraffin-embedded, formalin-fixed specimens of 70 patients with stage II colorectal cancer. Epidemiological and survival data were blinded from the microsatellite analysis to avoid bias. RESULTS: The average follow-up time was 63.3 months for all patients. Eleven patients died of colorectal cancer by the end of the study. Loss of heterozygosity of 18q21 was present in 30 of 70 (43%) tumors. After adjustment for all other evaluated factors, 18q21 allelic loss was not a predictor of survival (hazard ratio, 1.17; 95% confidence interval, 0.27-5.10; P = 0.84). CONCLUSIONS: Loss of heterozygosity of 18q21 does not seem to predict a survival disadvantage in stage II colorectal cancer in our patient population, and its proposed use as a prognosticator of survival or chemotherapy stratification marker for stage II tumors is not substantiated.

Aged↗