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Flow cytometry and squamous cell carcinoma of the maxillary sinus: A possible prognostic indicator for multimodality intervention.

Malignant tumors of the paranasal sinuses constitute less than 1% of all malignancies. Unfortunately, few prognostic factors have been identified regarding the efficacy of interventional therapy. Patients with carcinoma of the maxillary sinus frequently present with an advanced stage of disease and multimodality therapy is often proposed. Although some tumors appear to be more sensitive to preoperative chemotherapy and radiation therapy, a method of predicting and evaluating tumor behavior has not been recognized. Introduced as a means of identifying cell populations with abnormalities in total DNA content, flow-cytometric DNA analysis provides a quick and reliable means of tumor characterization for many malignancies. Although nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types, current data on the role of DNA content in head and neck carcinoma is conflicting and incomplete. To evaluate the role of flow-cytometric DNA analysis in predicting therapeutic alternatives, 22 patients with squamous cell carcinoma of the maxillary sinus were reviewed. Patient outcome and histopathologic grade were retrospectively compared with flow-cytometric evaluations of paraffin-embedded formalin-fixed tumor specimens. Four of sixteen tumors (25%) were found to be aneuploid and were also associated with an increased survival rate (p < 0.01). This initial data emphasizes the possible usefulness of DNA measurement for characterization of squamous cell carcinoma of the maxillary sinus and stresses the need for further evaluation.

Adult↗

Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure.

OBJECTIVE: To find out whether changes in the daily prothrombin time are of prognostic importance in patients with paracetamol induced fulminant hepatic failure. DESIGN: Retrospective study. SETTING: The Liver Unit, King's College Hospital, London. PATIENTS: 150 Consecutive patients with paracetamol induced fulminant hepatic failure admitted between October 1986 and February 1989. MAIN OUTCOME MEASURE: Death. RESULTS: Of the 150 patients, 72 (48%) died. In all, 34 of the 37 (92%) patients with a peak prothrombin time of greater than or equal to 180 seconds died as did 20 of the 41 (49%) with a time of 130-179 seconds, nine of the 25 (36%) with a time of 90-129 seconds, and nine of the 47 (19%) with a time of less than 90 seconds. Of the 42 patients with a continuing rise in prothrombin time between days 3 and 4 after overdose, 39 died (93%) compared with 21 of the 96 (22%) in whom the prothrombin time fell. CONCLUSIONS: These data indicate that a continued increase in prothrombin time on day 4 after overdose and a peak prothrombin time of greater than or equal to 180 seconds identify at an early stage those patients with a less than 8% chance of survival. Liver transplantation should be considered in patients meeting either of these criteria.

Acetaminophen↗

Blood lactate levels are better prognostic indicators than TNF and IL-6 levels in patients with septic shock.

OBJECTIVE: Both serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) and blood lactate levels in patients with septic shock have been shown to correlate with prognosis. The aim of the study was to define the relative predictive value of these measures. PATIENTS: 38 hospitalized patients with septic shock, including 18 survivors and 20 non-survivors. INTERVENTION: Blood TNF alpha (immunoradiometric assay), IL-6 (bioassay) and lactate (enzymatic method) levels were serially measured at the onset of septic shock and after 24 and 48 h. RESULTS: TNF alpha levels tended to be higher in the non-survivors than in the survivors at the onset of shock (204 +/- 392 vs 129 +/- 195 pg/ml, p = NS) but decreased similarly in both groups with time (p = 0.03). IL-6 levels at admission were highly variable (9656 +/- 19851 U/ml in the non-survivors and 69,222 +/- 248,804 U/ml in the survivors). Log IL-6 decreased similarly in both groups with time (p = 0.004). Admission blood lactate levels were higher in the non-survivors than in the survivors (6.11 +/- 4.78 mEq/l vs 3.49 +/- 2.00 mEq/l, p < 0.05) and decreased significantly with time in all patients (p = 0.024). However, this decrease was greater in the survivors than in the non-survivors (p = 0.003). CONCLUSION: These data indicate that the large variability in TNF alpha and IL-6 levels limit their prognostic significance in patients with septic shock. The predictive value of the trend in cytokine levels over time is not superior to that of trends in blood lactate levels.

Adult↗

Serial measurement of arterial lactate concentrations as a prognostic indicator in relation to the incidence of disseminated intravascular coagulation in patients with systemic inflammatory response syndrome.

To demonstrate the prognostic value of measuring blood lactate concentrations and to investigate the mechanisms of lactate production in patients with systemic inflammatory response syndrome (SIRS), we conducted a prospective cohort study. Among 22 patients with SIRS, there were 9 survivors and 13 nonsurvivors. Serial arterial lactate concentrations were measured on the day of admission to the intensive care unit (day 0). then on days 1-4. The subjects of this study consisted of 14 patients with SIRS, 6 with severe sepsis, and 2 with septic shock. On admission, the lactate concentrations did not differ between the two groups, but remained high in the nonsurvivors throughout the study period, while they progressively decreased in the survivors. The incidence of disseminated intravascular coagulation (DIC) was significantly higher in the nonsurvivors than in the survivors. The nonsurvivors had persistently higher DIC scores and lower platelet counts than the survivors. The changes in lactate concentration over time were statistically different between the patients with DIC and those without DIC. The findings of this study clearly demonstrated that serial arterial lactate measurements can predict a poor outcome in patients with SIRS, severe sepsis, or septic shock. DIC might play an important role in the pathogenesis of lactate production in these newly defined critically ill patients.

Analysis of Variance↗

Human papillomavirus deoxyribonucleic acid as a prognostic indicator in early-stage cervical cancer: a possible role for type 18.

OBJECTIVE: Our purpose was to determine the prognostic significance of human papillomavirus deoxyribonucleic acid in cervical cancers. STUDY DESIGN: The polymerase chain reaction was used to detect human papillomavirus deoxyribonucleic acid types 6, 11, 16, 18, 31, 33, 52, or 58 in tumors from 148 patients (equal numbers of whom were disease free or had relapses) surgically treated for stage IB or IIA cancers in a major Australian hospital. Cox regression modeling was used to assess the effect of human papillomavirus status on tumor recurrence, taking into account patient age, clinical stage, histologic node status, and type of tumor. RESULTS: Seventy of 74 (95%) of the recurring tumors and 62 of 74 (84%) of the nonrecurring tumors were human papillomavirus deoxyribonucleic acid positive. The rates of positivity of types 16 and 18 were 64% versus 31% in the recurrers and 65% versus 14% in the nonrecurrers. Human papillomavirus type 18 positivity was associated with a greater risk of recurrence than was type 16 positivity (hazard ratio 1.8; p = 0.03). Clinical stage, nodal metastasis, and young age (< or = 35 years) also had adverse effects on relapse (hazard ratio for each approximately 2). CONCLUSION: Human papillomavirus type 18 positivity is a risk factor for tumor recurrence in surgically treated cervical cancer.

Adult↗

Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy.

PURPOSE: To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy. METHODS AND MATERIALS: Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m(2)/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m(2)) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system. RESULTS: Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically significant prognosticators of disease-specific survival and relapse-free survival. pCR Stage T4 disease was a strong predictor of local recurrence. The 5-year local control rate was 98% for pCR T0-T2, 89% for pCR T3, and 65% for pCR T4 disease (p = 0.00044). In multivariate analysis, the pCR TNM stage was the most statistically significant independent predictor of survival (p = 0.003) and relapse-free survival (p < 0.001). CONCLUSION: For patients who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, the pCR TNM stage was a strong prognosticator of recurrence and survival. It can be used to identify high-risk patients for additional postoperative therapy.

Adult↗

Sociodemographic factors and quality of life as prognostic indicators in head and neck cancer.

Pre-treatment quality of life (QOL) has been found to be an independent prognostic factor for survival in cancer patients, in particular in patients with advanced cancer. Sociodemographic factors such as marital and socioeconomic status have also been recognised as prognostic factors. We studied the influence of QOL and mood (measured with the European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the Head and Neck Cancer Questionnaire (EORTC QLQ-H&N35), and with the Center for Epidemiologic Studies-Depression Scale (CES-D)) as measured before treatment, the use of cigarettes and alcohol and sociodemographic factors (age, gender, marital status, income and occupation) on recurrence and survival in 208 patients with head and neck cancer prior to treatment with surgery and/or radiotherapy, using Kaplan-Meier and Cox regression analyses. Cognitive functioning and, to a lesser degree, marital status were independent predictors of recurrence and survival, along with medical factors (stage and radicality). Patients with less than optimal cognitive functioning and unmarried patients had a relative risk (RR) of recurrence of 1.72 (95% confidence interval (95% CI) 1.01-2.93) and 1.85 (95% CI 1.06-3.33), respectively, and a RR of dying of 1.90 (95% CI 1.10-3.26) and 1.82 (95% CI 1.03-3.23), respectively. Performance status, physical functioning, mood and global QOL and smoking and drinking did not predict for recurrence and survival. The influence of cognitive functioning might be related to the use of alcohol. Marital status may influence prognosis through mechanisms of health behaviour and/or social support mechanisms.

Alcohol Drinking↗

Histologic features are important prognostic indicators in early stages lung adenocarcinomas.

This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and < or = 5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and > 5 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm+pure invasive groups (groups III, IV), and the < 5 mm + noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma.

Adenocarcinoma↗

Alveolar--capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure.

AIMS: Lung dysfunction occurring in chronic heart failure worsens clinical status and exercise performance. The prognostic value of airway and alveolar function measurements in chronic heart failure has not been explored. We aimed to evaluate the prognostic value of lung function tests in a population of patients with stable chronic heart failure. METHODS AND RESULTS: One hundred and six stable chronic heart failure patients (whose left ventricular ejection fraction averaged 33 +/- 1%) underwent echocardiography, metabolic stress testing, assessment of pulmonary function at rest (by spirometry), of alveolar diffusing capacity (DLco) (with carbon monoxide technique) and of its membrane (DM) and capillary blood volume (Vc) components. Prognostic relevance of pulmonary variables was assessed by the Kaplan-Meier approach with log-rank testing and by Cox regression analysis. Cut-off values of lung parameters were based on the 33rd and 66th centiles. Seventeen patients died for cardiac reasons. Non-survivors compared to survivors showed lower forced expiratory volume in 1 s (2 X 1 +/- 0 X 1 vs 2 X 4 +/- 0 X 1 l; P<0 X 01), forced vital capacity (2 X 6 +/- 0 X 1 vs 2 X 9 +/- 0 X 1 l; P<0 X 01), maximal voluntary ventilation (80 X 7 +/- 2 X 5 vs 95 X 4 +/- 2 X 7 l; P<0 X 01), DLco (16 X 5 +/- 1 X 1 vs 19 X 3 +/- 0 X 6 ml . min(-1) . mmHg(-1); P<0 X 01) and DM (25 X 1 +/- 1 X 8 vs 31 X 9 +/- 1 X 5 ml . min(-1) . mmHg(-1); P<0 X 01). They also exhibited a smaller peak VO2 (14 X 6 +/- 0 X 7 vs 15 X 9 +/- 0 X 6 ml . min(-1) . kg(-1); P<0 X 05) and a steeper VE/VCO2 slope (45 X 0 +/- 1 X 7 vs 41 X 9 +/- 1 X 5; P<0 X 01). Multivariate analysis revealed that DM was the only independent predictor of cardiac death. Cases at high risk for adverse outcome were identified by a DM<24 X 7 ml . min(-1) . mmHg(-1). Patients receiving ACE-inhibitors presented with a higher DM (32 X 1 +/- 1 X 7 vs 27 X 9 +/- 1 X 7 ml . min(-1) . mmHg(-1), P<0 X 05) as well as a better Cox estimated survival rate. CONCLUSIONS: Impaired DM is a powerful independent predictor of worse prognosis in stable chronic heart failure and may be considered an additional index of disease severity, as well as a specific therapeutic target.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical and pathological prognostic indicators with colorectal mucinous carcinomas.

BACKGROUND/AIMS: Colorectal mucinous carcinomas are considered to have a worse prognosis than typical adenocarcinomas. To evaluate the prognostic relevance of a series of clinical and pathological variables, patients with colorectal mucinous carcinomas were studied retrospectively. METHODOLOGY: Ninety-eight patients who underwent surgery for colorectal mucinous carcinomas were included in this study. We firstly examined whether signet-ring cell carcinomas exhibited worse prognosis than the other mucinous carcinomas. Prognostic factors were then analyzed by both univariate and multivariate analysis for 70 patients who underwent complete resection. RESULTS: The overall five-year survival rate was 44%. Amount of signet-ring cells was a non-significant indicator of poor prognosis. For the cases whose cancers were completely resected, four parameters (liver metastasis, lymph node involvement, vessel involvement, spread beyond the bowel wall) were significantly related to prognosis on univariate analysis. With the multivariate analysis, liver metastasis and spread beyond the bowel wall were independent variables. CONCLUSIONS: This study reaffirmed the importance of liver metastasis and spread beyond the bowel wall for prediction of prognosis with colorectal mucinous carcinomas for cases who undergo complete resection. In addition, the presence of signet-ring cells is a non-significant indicator of a poor prognosis.

Adenocarcinoma, Mucinous↗

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center.

BACKGROUND: The current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma. METHODS: From the Sydney Melanoma Unit database, 3661 patients with complete clinical information and details of primary tumor thickness, ulcerative state, and TMR were studied. TMR was expressed as mitoses per mm(2) in the dermal part of the tumor in which most mitoses were seen, as recommended in the 1982 revision of the 1972 Sydney classification of malignant melanoma. To determine which was the more prognostically useful method of grouping TMR, two separate methods (A and B) were used. Factors predicting melanoma-specific survival were analyzed using the Cox proportional hazards regression model. RESULTS: Patients with a TMR of 0 mitoses/mm(2) had a significantly better survival than those with 1 mitosis/mm(2) (P < 0.0001) but no significant survival differences were recorded for the stepwise increases from 1-2, 2-3, 3-4, and 4-5/mm(2). Tumor thickness, ulceration, and TMR were closely correlated, whether TMR was grouped using Method A (0, 1-4, 5-10, and >/= 11 mitoses/mm(2)) or Method B (0-1, 2-4, and >/= 5 mitoses/mm(2)). However, Cox regression analysis indicated that the TMR was a highly significant independent prognostic factor, particularly when grouped according to Method A, in which it was second only to tumor thickness as the most powerful predictor of survival (P < 0.0001). CONCLUSIONS: TMR is an important independent predictor of survival for melanoma patients. If confirmed by studies from other centers, it has the potential to further improve the accuracy of melanoma staging, as well as to define more rigidly the risk categories for patients entering clinical trials.

Adolescent↗

Tumor size as a simple prognostic indicator for gastric carcinoma.

BACKGROUND: Tumor size can be measured easily before or during operation with no special tools, but its prognostic use in patients with gastric carcinoma is still unclear. METHODS: Clinicopathologic data of 479 patients who underwent curative operation for gastric carcinoma were studies. The relationship between tumor size and survival of patients was investigated. RESULTS: The patients were divided into three groups: 182 with tumors measuring < 4 cm (group I), 252 with tumors of 4-10 cm (group II), and 45 with tumors of > or = 10 cm (group III). The 10-year survival rates for group I, II, and III patients were 92%, 66% and 33%, respectively (p < 0.01), and the three groups were significantly different with regard to depth of invasion (p < 0.01), number and level of lymph node metastasis (p < 0.01), and stage of disease (p < 0.01). Multivariate analysis indicated that tumor size independently influenced the survival of patients. CONCLUSIONS: Tumor size clinically serves as a simple predictor of tumor progression and survival of patients in gastric carcinoma.

Adenocarcinoma↗

Tumor vascularity as a prognostic indicator in intermediate-thickness (0.76-4 mm) cutaneous melanoma. A quantitative assay.

Tumor vascularity has been reported to be a prognostic factor in solid tumors. We studied the prognostic value of tumor vascularity in 19 primary stage I skin melanomas. Only intermediate-thickness melanomas (0.76-4.00-mm thick) were studied. They were treated surgically to provide two groups of patients. The first group of 11 patients had no evidence of metastases after a follow-up of a mean period of 72.36 months, whereas the second one developed metastases in a mean period of 46.87 months. The two groups were matched for important prognostic factors including tumor thickness, sex, and age. Vascularity was quantified by a morphometric stereological analysis on paraffin sections stained with anti CD31 monoclonal antibody. The percentage of vascular area was significantly higher in the metastasizing group than in the nonmetastasizing one. Our study suggests that increased vascularity may have a prognostic significance in intermediate-thickness melanoma.

Female↗

Prognostic indices to predict survival of first and second renal allografts.

In order to predict kidney graft survival, the influence of independent prognostic factors can be examined multivariately and the factors combined into a prognostic index. Data on 7121 patients receiving an unrelated first and 1033 patients receiving an unrelated second transplant from nonliving donors, between 1 January 1984 and 31 December 1987, were analyzed to ascertain the most important prognostic variables up to 4.5 years posttransplantation. Factors found to be significant for graft survival were donor and recipient age and sex, recipient blood group, whether the recipient was diabetic, cold ischemic period, number of HLA-B and - DR mismatches, highest percent panel-reactive antibody, transplant center, and--for second transplants--duration of first graft. A risk score for graft failure, based on the prognostic factors, was developed using these factors and five risk groups (from excellent to very poor prognosis) were identified. This index was tested on an independent data set and showed a good fit when compared with the observed Kaplan-Meier graft survival: patients allocated by the risk score into the "excellent prognosis" group had an observed one-year graft survival of 90.4%, compared with a predicted value of 90.3% for first transplants. Corresponding results for second transplants were 86.2% (observed) and 86.0% (predicted). For the "very poor" prognosis group, the results were 73.4% (observed) and 74.4% (predicted), for first transplants, and 60.9% (observed) and 60.1% (predicted), for second transplants. A prognostic index can therefore identify patients likely to have a high or low graft survival, leading to improved decision-making and aiding the choice of patient management once a recipient has been transplanted.

ABO Blood-Group System↗

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.

Adult↗

Prognostic indicators for poor risk epithelial ovarian carcinoma.

BACKGROUND: The objective of this study was to identify factors that categorize patients with epithelial ovarian carcinoma into favorable and unfavorable prognostic groups at the time of initial treatment. METHODS: Data were analyzed from 51 women who were treated at Yale University, had an evaluable CA 125 half-life (t1/2), and were followed for disease recurrence for at least 2 years. RESULTS: Grade, maximum level of CA 125, and histology did not provide useful prognostic information. Stage, residual disease, minimum CA 125, and CA 125 t1/2 individually were predictive of persistent disease or recurrence within 3 years of diagnosis with sensitivities of 97, 70, 34, and 49%, respectively, and specificities of 33, 83, 100, and 83%, respectively. When these factors are combined, defining an unfavorable prognostic group as those patients having residual disease greater than 1 cm, CA 125 t1/2 greater than 12 days, or minimum CA 125 never falling below 35 U/ml, sensitivity and specificity were 96 and 65%, respectively, at 1 year of follow-up and 91 and 75%, respectively, at 3 years of follow-up. 75%, respectively, at 3 years of follow-up. CONCLUSIONS: In those patients in whom residual small volume disease after primary surgery indicates a good prognosis, minimum CA 125 and CA 125 t1/2 during chemotherapy can further categorize patients into favorable and unfavorable prognostic groups.

Antigens, Tumor-Associated, Carbohydrate↗

The Child-Pugh classification as a prognostic indicator for survival in primary sclerosing cholangitis.

Clinical decisions in primary sclerosing cholangitis (PSC) depend upon understanding its variable natural history. Several prognostic models for survival have been developed. We explored the Child-Pugh Classification (CPC) to determine if it predicts survival as well as a disease-specific model (DSM). We identified 208 PSC patients who satisfied established criteria. Prognostic variables were measured from the first visit. Kaplan-Meier survival estimates were obtained for CPC twice, once censoring observations at orthotopic liver transplantation and again considering orthotopic liver transplantation as a failure. A stepwise Cox proportional hazards-model was used to identify the factors associated with mortality. For 208 patients, the mean follow-up was 70 months (SD + 55). Kaplan-Meier 7-year survivals for CPC A, B, and C were 89.8%, 68%, and 24.9%, respectively (P < .001). The Cox model identified CPC and age as the most significant predictors of mortality. Adding the DSM risk score did not significantly improve the fit of the model (P = .75). The following were concluded: 1) CPC is a powerful predictor of survival in PSC; 2) DSM does not enhance the predictive ability of CPC; and 3) CPC may be used as an alternative to the DSM in research studies and clinical decision-making.

Adult↗

Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, Ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator.

Although aberrant expression of several cell-cycle regulators has been reported in endometrial carcinoma, correlations among these factors and their prognostic significance have not fully been elucidated. In the present study, expression of cyclins (D1, E, A, and B1), cyclin-dependent kinases (cdk2, cdk4, and cdc2), and tumor-suppressor gene products (p53, p21, and p27) were systematically examined by immunohistochemistry in 82 cases of endometrial carcinoma and 20 normal endometria. Results were compared with the expression of Ki-67, sex steroid receptor status, clinicopathological parameters, and patient outcomes. Positive staining for cyclin D1, cyclin E, cyclin A, cyclin B1, cdk2, cdk4, cdc2, p53, p21, and p27 was observed in 63%, 66%, 31%, 32%, 51%, 77%, 71%, 43%, 35%, and 60% of the 82 carcinomas, respectively. Among these factors, positive staining for cyclin D1, cdk4, and p53 was significantly frequent in advanced-stage tumors, and that for cyclin D1, cyclin A, cdk4, p21, and p53 was more frequent in higher-grade tumors. High correlation was found between cyclin A and p53 expression, between cyclin D1 and cdk4 expression, between cdk4 and Ki-67 expression, and between p21 and Ki-67 expression. Multivariate analysis showed that the factors for poor prognosis were advanced stage and cyclin A positivity. These findings suggest that various cell-cycle regulators are involved in activated cell growth of endometrial carcinoma, and that positive staining for cyclin A could be a useful marker for unfavorable patient prognosis.

Adenocarcinoma↗