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Prognostic factors of surgical resection in middle and distal bile duct cancer: an analysis of 55 patients concerning the significance of ductal and radial margins.

BACKGROUND: The surgical outcome of middle and/or distal bile duct cancer remains unsatisfactory. Although the resectional margin is known to be a predictive factor, the prognostic significance of a positive ductal margin and other radial margin has never been evaluated independently. METHODS: The clinicopathologic data of 55 patients who had undergone surgical resection for middle and/or distal bile duct cancer between 1987 and 2003 were reviewed retrospectively. The surgical procedures consisted of pancreatoduodenectomy in 42 patients (76%), extrahepatic bile duct resection in 8 patients (15%), major hemihepatectomy (Hx) in 3 patients (5%), and pancreatoduodenectomy plus Hx in 2 patients (4%). In all the patients, intraoperative diagnosis of the ductal margins was performed using frozen sections. Twenty-one clinicopathologic factors, including the status of the ductal margins and of other radial margins, were evaluated using univariate and multivariate analyses. RESULTS: The overall 5-year survival rate and the median survival time were 24% and 38 months, respectively. There were 4 (7%) postoperative deaths. Fifteen of the remaining 51 patients (29%) were determined to have positive hepatic-side ductal margins during operation, and 14 of them underwent additional resection of the bile duct (1.6[range, 1-3] times, on average). As a result, hepatic-side ductal margin (hm) and duodenal-side ductal margin were found to be positive in 6 and 0 patients on the final pathologic analysis, respectively. Two of the 6 patients (33%) with positive hm have developed ductal recurrence so far, but the status of hm was not found to be a significant predictor. The depth of neoplastic invasion into the bile duct wall, pancreatic invasion, radial margin, and blood transfusion were significant prognostic factors by the univariate analysis. Multivariate analysis revealed that the depth of neoplastic invasion and blood transfusion were the independent prognostic factors. CONCLUSIONS: In the treatment of middle and distal bile duct cancer, it is of importance to secure a negative radial margin, although it may be less beneficial to obtain a negative hm. Surgeons should make efforts to obtain negative radial margins and to avoid blood transfusion.

Adult↗

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients.

PURPOSE: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. MATERIALS AND METHODS: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. RESULTS: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic factors in our material, although with lesser importance. In patients with lung primaries, sex was found to have significant impact on survival. In patients with breast primaries, interval between primary tumor and development of brain metastases appeared to be a statistically significant prognostic factor. Histology in patients with lung primaries and distribution of brain metastases were not found to be statistically significant in multivariate analysis. CONCLUSIONS: In this large database, the value of established prognostic factors was confirmed and, furthermore, some less well-recognized parameters such as response to steroid treatment, serum lactate dehydrogenase, age, sex in lung primaries, and site of primary tumor were established. From the three strongest prognostic factors--performance status, response to steroids, and evidence of systemic disease--simple identification of favorable and unfavorable subgroups of patients with brain metastases can be constructed.

Adolescent↗

[Analysis of prognostic factors of node negative breast cancer].

Prognostic factors of 229 patients with node negative breast cancer were analysed using Cox's proportional hazard regression model. From 11 pathological factors, four factors nuclear grade, pectoral invasion, fat infiltration and tumor size were selected under condition of p less than 0.05. When the three factors (moderate or poorly differentiated nuclear grade, marked fatty infiltration and tumor size 2 cm) were provided as poor prognostic factors, node negative breast cancer was successfully classified from the number of the poor prognostic factors: namely, the recurrence rate of subgroups with the number of 0,1,2,3 was 2%, 7%, 21%, 39%, respectively.

Breast Neoplasms↗

Prognostic factors in sterile pancreatic necrosis.

Although the overall mortality in sterile pancreatic necrosis is low, patients who experience systemic complications may have a higher mortality. To study the impact of systemic complications and other factors on survival, possible prognostic factors were evaluated among 26 patients who experienced at least one systemic complication. Mortality was 38%. Factors that correlated with a fatal outcome were high Ranson's scores during the first 48 hours (P = 0.01), high APACHE-II scores at admission (P = 0.04) and at 48 hours (P = 0.03), shock (P < 0.001), renal insufficiency (P < 0.05), multiple systemic complications (P < 0.001), and high body mass index (P = 0.01). Most systemic complications occurred during the first 2 weeks of illness. Logistic regression analysis showed that shock was the best predictor of a fatal outcome. Patients with favorable prognostic factors survived whether treated medically or surgically, whereas those with unfavorable factors had a fatal outcome whether treated medically or surgically. It is concluded that patients with severe sterile necrosis have a high mortality rate and that shock and other prognostic factors identify which patients are most likely to have a fatal outcome.

Adult↗

[Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia].

Prognostic significance of disease features obtained at the time of initial diagnosis was analyzed in 90 patients with chronic myelogenous leukemia (CML) in chronic phase. Median survival of this population was 45.9 months. Univariate analysis revealed that splenomegaly, bone marrow basophils, bone marrow blasts, peripheral blood blasts, and bone marrow eosinophils were significant prognostic factors for survival, and that peripheral blood leukocytes counts, hemoglobin concentration, performance status, age and lymphadenopathy were factors with border line significance. There were multiple interrelationship among these disease features. Multivariate regression analysis identified that age, hemoglobin concentration, and bone marrow blasts were independent primarily significant prognostic factors for survival. The Cox model generated with three variables of age, hemoglobin concentration, and percent blasts in bone marrow provided a useful representation of risk status in the population. A hazard function derived from the patients population segregated patients into three groups with significantly different survival patterns: A lower risk group, an intermediate group and a high risk group of patients with median survival of 57.8, 49.8 and 38.4 months respectively. Survival after CML blast crisis was short and overall median survival of 54 patients with CML blast crisis was 6.4 months. A sole prognostic factor for survival in blast crisis identified by multivariate analysis was blast cell type at CML blast crisis and patients with lymphoid phenotype had a good prognosis with median survival of 9.8 months. Median survival of myeloid crisis was 4.2 months. No other disease features were identified as significant prognostic factors in the present patient population.

Adult↗

Intraocular foreign bodies: management, prognostic factors, and visual outcomes.

OBJECTIVE: To determine prognostic factors and visual outcomes in patients with intraocular foreign bodies (IOFBs). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Fifty-nine consecutive patients undergoing removal of an IOFB with a minimum of 6 months of follow-up. INTERVENTION: Surgical removal of the IOFB and repair of associated ocular trauma. MAIN OUTCOME MEASURES: Final best corrected visual acuity was the main outcome measured. Ocular findings at presentation were compared with final visual acuity to determine prognostic factors for visual outcome. RESULTS: Final best corrected visual acuity of 20/40 or more was obtained in 42 patients (71%) and ambulatory vision (>5/200) was achieved in 50 patients (85%). Presenting visual acuity was predictive of final visual outcome (P < 0.01). Prognostic factors for a better visual outcome (P < 0.05) included better presenting visual acuity and hammering metal on metal as the mechanism of injury. Prognostic factors for a poor outcome (P < 0.05) included poor presenting visual acuity, the presence of an afferent pupillary defect, and vitreous hemorrhage. CONCLUSIONS: Final visual outcomes were excellent in 71% of patients. Presenting visual acuity was the strongest predictor of final visual outcome in this series. Additional predictive factors included the mechanism of injury, the presence of an afferent pupillary defect, and vitreous hemorrhage.

Adolescent↗

Yearly alterations in prognostic factors in gastric cancer during the post-operative period.

BACKGROUND: Prognostic factors in gastric cancer may alter with time after surgery. Ascertaining prognostic factors appropriate for each post-operative year should contribute to the establishment of better therapeutic strategies and ultimately to the improvement of their long-term results. PATIENTS AND METHODS: In the present study, in order to elucidate whether prognostic factors would alter annually, cause of death, recurrence patterns and prognostic factors of gastric cancer by uni- and multivariate analysis were evaluated retrospectively in 833 consecutive patients who underwent potentially curative gastrectomy. RESULTS: During the first 2 years, the prognostic factors were age, T3-4, pN3, tumor diameter and number of metastatic lymph nodes. During the 3rd and 4th years, they were age, pN2 and number of metastatic lymph nodes; for the fourth year, age and number of metastatic lymph nodes; for the fifth year, age alone. Peritoneal recurrence was predominant throughout the post-operative period, but its incidence decreased gradually with time. The incidence of hematogenous recurrence increased while that of lymphatic recurrence did not change with time. CONCLUSION: As prognostic factors change over time, appropriate alterations to therapeutic strategy should be established for each successive period. Particularly, effective therapeutic strategy for peritoneal metastasis should be established in patients with a high number of metastatic lymph nodes during the first five years. Moreover, the treatment of concomitant disease and the evaluation of other malignant disease should be continued after the 5th year.

Cause of Death↗

Prognostic factors in cancer.

Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

Humans↗

[Prognostic factors in epitheliomas of the breast].

Prognostic factors in breast carcinoma were studied on material which consisted of 733 patients with a follow-up of over 5 years and on 361 with a follow-up of over 10 years. In the first part of the study the prognostic factors are related to the physical characteristics of the primary tumour such as its situation and size and its relationship to skin and deep tissues. Clinical examination of the axilla, studied in detail, has proved a reliable guide to prognosis. The second part deals with such factors as age, hormonal status, age at first pregnancy and parity. A critical analysis of the T.N.M. classification ends the study, with special reference to the prognostic factors which relate to the primary tumour.

Adult↗

Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I--an independent prognostic factor.

The aim of this study was to exploit the potential clinical use of circulating cytokine measurements in colorectal cancer (CRC) patients. The levels of cytokines and cytokine receptors were assessed by ELISA in the sera of 50 healthy volunteers and 157 patients with previously untreated CRC and then related to clinicopathological features and prognosis. All tumors were verified histologically as colorectal adenocarcinomas and staged according to TNM classification. The levels of circulating interleukin (IL)-6, IL-8, macrophage colony-stimulating factor (M-CSF) and interleukin 1 receptor antagonist (IL-1ra) significantly increased with the clinical stage of CRC, and the levels of IL-6, soluble tumor necrosis factor (sTNF) receptor type I (RI), soluble interleukin 2 receptor alpha and TNFalpha with tumor grade, while IL-6, IL-8, M-CSF, IL-1ra and sTNF RI levels significantly rose with bowel wall invasion. None of the cytokine or soluble cytokine receptor levels were influenced by age, gender and colon versus rectum localization. sTNF RI, IL-8, IL-6 and vascular endothelial growth factor measurements demonstrated the highest diagnostic sensitivity. sTNF RI was found elevated in the greatest percentage of all CRC patients, in the greatest proportion of stage I patients and presented the best diagnostic sensitivity. In addition, the sTNF RI level strongly correlated with tumor grade and invasion and proved to be an independent prognostic factor.

Adult↗

Adjuvant anthracycline therapy as a prognostic factor in metastatic breast cancer.

BACKGROUND: Prognostic factors in metastatic breast cancer continue to be identified. Previous adjuvant chemotherapy appeared to have poor prognosis in some studies but, despite this, the prior use of anthracyclines in the adjuvant setting has not been clearly established as an adverse prognostic factor once metastatic disease develops. PATIENTS AND METHODS: Patients (n = 1,436) with stages I-IIIa breast cancer were surgically treated with/without radiotherapy and/or systemic adjuvant treatment. Of these, 297 patients who relapsed with metastatic disease constitute the sample population of this retrospective study. Survival, as a function of time since diagnosis of metastatic disease, was assessed in relation to the following factors: age, size of the primary tumor, grade, number of positive axillary nodes, type of surgery, type of adjuvant treatment administered, time to relapse, number of metastatic sites, presence of visceral metastases and type of treatment employed at the time of relapse. RESULTS: In multivariable analysis three factors remained significant predictors of short survival time: more than 1 site of metastases (p = 0.00003), shorter time to relapse (p = 0.003) and the previous administration of anthracyclines as adjuvant therapy (p = 0.005). CONCLUSIONS: The prior use of adjuvant anthracyclines, with other known clinical prognostic factors, confers a poorer outcome in metastatic disease, perhaps as a result of resistant clones selection or by induction of de novo resistance.

Antibiotics, Antineoplastic↗

Vascular endothelial growth factor (VEGF) in astrocytic gliomas--a prognostic factor?

Survival in astrocytic gliomas is closely related to WHO tumor grade. Within one tumor grade, especially in grade II and III tumors, the clinical course is variable and can hardly be predicted by histological criteria. Neovascularization is a neuropathological hallmark in high grade gliomas and angiogenic factors may play an important role in malignant tumor progression. Therefore, 162 primary astrocytic gliomas (57 astrocytomas WHO grade II, 27 astrocytomas WHO grade III and 78 glioblastomas WHO grade IV) were investigated immunohistochemically for expression of vascular endothelial growth factor (VEGF), which is considered to represent the main angiogenic factor in astrocytic gliomas. Clinical data known to influence prognosis were documented. VEGF expression was found in 21 of 57 astrocytomas WHO grade II (36.8%), in 18 of 27 astrocytomas WHO grade III (66.7%) and in 50 of 78 glioblastomas (64.1%). A strong correlation between VEGF expression and survival was found within the whole study group, however, within one tumor grade no such correlation was obvious. In a multifactorial analysis VEGF expression was not found to be an independent prognostic factor in astrocytic gliomas.

Adult↗

Surgical treatments of chronic idiopathic thrombocytopenic purpura and prognostic factors for splenectomy.

To determine the prognostic factors for splenectomy in patients with chronic idiopathic thrombocytopenic purpura (ITP), 26 consecutive patients who had undergone splenectomy as a treatment for ITP in the last 20 years were investigated retrospectively. Predictive values of age, sex, the interval between diagnosis and surgery, presence of antiplatelet antibodies or accessory spleen, bleeding time, response to corticosteroids, response to high-dose immunoglobulin, weight of spleen, serum platelet-associated immunoglobulin G, preoperative maximal platelet count, and preoperative minimal platelet count were examined with multivariate analysis by multiple regression. Age less than 50 years at surgery, platelet count of 100 x 10(9)/l or more in response to high-dose immunoglobulin, and a maximal platelet count of 100 x 10(9)/l or more before splenectomy were favorable prognostic factors (p < 0.05). The correlation coefficient, sensitivity, specificity, and positive-predictive value of the analyzed multiple regression based on prognostic factors were 0.885, 68.8%, 85.7% and 91.7%, respectively. In conclusion, splenectomy is an effective treatment for younger patients, large maximal preoperative platelet counts and preoperative immunoglobulin dependence. Multivariate function analysis was useful for predicting outcome.

Adolescent↗

[Prognostic factors of advanced colorectal cancers].

Prognostic factors have been so far much more extensively studied for resectable colorectal cancers than for advanced colorectal cancers. However, the recent increase in treatment possibilities forces physicians to take into account the prognostic factors of patients with advanced colorectal cancer. The prognostic evaluation of these patients is still mostly based on clinical parameters, such as performance status and allocated treatment. More recently, the prognostic role of biological parameters such as p53 gene or enzymes implicated in 5-fluorouracil metabolisms has been identified.

Colorectal Neoplasms↗

Prognostic factor studies in oncology: osteosarcoma as a clinical example.

OBJECTIVE: Prognostic factor studies are abundant in oncology. Nevertheless, most of them have very limited impact on clinical practice, in part because many of them have a low statistical power. The importance of statistical power is illustrated using bootstrap resampling of data from a series of osteosarcoma patients. METHODS AND MATERIALS: Osteosarcoma is a rare disease, the incidence being just a few cases per million person-years in the Western World. Very few Phase III studies have been conducted in the disease, and much knowledge on therapeutic progress has come from Phase II studies. This has caused controversy concerning the validity of historical controls, which again has stimulated interest in the identification of prognostic factors in this disease. A literature search in the National Library of Medicine MEDLINE database was performed to identify prognostic factor studies in osteosarcoma published between 1975 and 1998. Monte Carlo methods, so-called bootstrap resampling, are used to investigate the importance of sample size based on survival data for a previously published series of 158 osteosarcomas treated with surgery alone. RESULTS: Most published studies are too small to provide useful information on prognostic factors in osteosarcoma. Three-quarters of the papers reviewed included less than 100 patients with osteosarcoma. More than 20 different potential prognostic factors were included in these papers. Inherent differences between studies and poor reporting hamper a synthesis of information from various studies. The results from the bootstrap resampling illustrate how the majority of published studies would miss even quite significant prognostic factors. CONCLUSIONS: An effort is needed to improve the design, conduct, and reporting of prognostic studies in oncology.

Bone Neoplasms↗

Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.

PURPOSE: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. EXPERIMENTAL DESIGN: EGFR mutations in exons 18 to 21 were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. RESULTS: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). CONCLUSIONS: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.

Adenocarcinoma↗

Time-dependence of hazard ratios for prognostic factors in primary breast cancer.

Some prognostic factors, such as steroid receptors, appear strongly related to outcome in early studies with short follow-up, but as follow-up matures the relationships appear to weaken. We investigated this phenomenon for several factors (tumor size, axillary lymph nodes, S-phase fraction, estrogen receptor (ER) status, and adjuvant therapy) in a large sample of breast cancer cases (N=2,873) with up to 17 years of follow-up for disease-free survival (DFS). Subjects in the study were identified from patients who had hormone receptor assays performed in our laboratory. Analysis of DFS included fitting a multivariate Cox proportional hazards model, testing for nonproportionality, and examining diagnostic plots. The assumption of proportional hazards was violated for several factors including ER, tumor size, and S-phase fraction. For ER, the hazard ratio was initially less than 1.0, indicating a good effect on prognosis, but increased at later times to values greater than 1.0, indicating a bad effect on prognosis. In contrast, the hazard ratios for tumor size and S-phase were initially high and decreased asymptotically toward 1.0 over time. Analysis of p53 expression in a subset of cases yielded qualitatively similar results. We conclude that several standard prognostic factors (ER, tumor size, S-phase fraction) and possibly other investigational factors have important but nonproportional effects on hazard. It is likely that violation of proportional hazards is common and not limited to breast cancer. Failure to recognize violations of proportional hazards can lead to both over- and under-estimation of the effects of important prognostic factors.

Adult↗

Nonlinear discriminant analysis and prognostic factor classification in node-negative primary breast cancer using probabilistic neural networks.

BACKGROUND: We used non-linear kernel discriminant analysis (KDA) to predict the outcome of 134 axillary node-negative primary breast cancer patients not treated with adjuvant therapy in a non censored database. MATERIAL: Posterior probabilities of relapse at 5 years were estimated using probabilistic neural networks (PNN) and a cross-validation (leave-one-out) technique to avoid overfitting the data. A stepwise method was used to construct the models to define the best combination of risk factors among eleven prognostic factors: age, menopausal status, Scarff-Bloom-Richardson grade, clinical tumor size, pathological tumor size, estrogen and progesterone receptor status, urokinase-type plasminogen activator, p53 protein level, c-erbB-2 protein and epidermal growth factor receptor. The different variables were tested individually and in combination to determine their prognostic power using a ROC indicator, which measures the separation between the probability distributions of the output neuron activations under the null hypothesis (no recurrence at 5 years) and under the alternative hypothesis (recurrence at 5 years). RESULTS: The best predictive one-dimensional model was obtained with uPA (ROC indicator = 0.75). A two-factor model including uPA and clinical tumor size (T) gave the best discrimination between recurrence and non recurrence at 5 years (ROC indicator = 0.84). Additional variables did not improve the accuracy of the prediction. The uPA-T model generated a map useful in predicting the posterior probability of cancer recurrence in a given patient. This representation allows the entire database to be easily visualized and each patient can be compared with the entire database. CONCLUSION: This is a powerful approach to analyze the impact of prognostic factors and it could find clinical applications in breast cancer.

Age Factors↗