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[Surgical treatment and evaluation of prognostic factors in spinal metastases of renal cell carcinoma].

AIM: The aim of this study was the evaluation of surgical results and prognostic factors in spinal metastases of renal cancer. METHODS: 37 surgical patients with spinal metastases of renal cell carcinoma were retrospectively analysed. In 2 patients the cervical, in 16 patients the thoracic, in 4 patients the thoraco-lumbar and in 16 patients the lumbar spine was involved. RESULTS: In 11 cases (29.7 %) a combined posterior-anterior spondylodesis with vertebral body replacement, in 26 cases (70.3 %) a single posterior instrumentation was done. Perioperatively, 24 complications appeared, 4 of them were lethal. Postoperatively, the neurological situation was unchanged in 26 patients, dischanged in 4 patients and improved in 7 patients. The level of pain was unchanged in 10 patients, dischanged in 3 patients and improved in 24 patients. The mean postoperative survival was 13.6 months. For the postoperative survival the Karnofsky-Index and the Frankel-Score were univariate highly significant, the factors nutritional condition and latency between the primary tumor and the development of spinal metastases showed a lower significancy. No prognostical influence for the postoperative survival could be detected for the factors gender, age, localisation of the metastases, type of operation and the factor solitary/multiple metastases. The multivariate analyses did not attempt any of the univariate significant prognostic factors for the postoperative survival. The postoperative survival was significantly (p: 0.0030) influenced by postoperative adjuvant therapy (radio- and/or chemotherapy). The analysis of each adjuvant therapy form (i. e. chemo-, radio- and combined therapy) attempts this prognostic effect (p: 0.0229). CONCLUSION: In most patients with spinal metastases of renal cell carcinoma, the singular posterior intrumentation combined with a decompression is a sufficient therapy. To avoid posterior implant failure, in patients with a prognosticated survival of more than one year, a combined posterior-anterior spondylodesis with vertebral body replacement should be done. The prognostic influence of an adjuvant postoperative treatment in the present study must be interpreted in the context of this small, highly selected patient collective. Further standardized studies should be performed to evaluate the prognostic influence of an adjuvant therapy.

Adult↗

[Proliferation index, axillary lymph node status, hormone receptors and age as prognostic factors in primary breast cancer].

A total of 233 primary carcinomas of the breast (n = 68 nodal negative and n = 165 nodal positive) of 77 woman patients of less than 50 years of age and pf 156 women patients of 50 years of age or older were examined for the prognostic significance of a proliferation index (in vitro chemoresistance assay). The prognostic significance of the proliferation index (high vs low proliferation) is compared with other prognostic factors that have already been in clinical use (age, axillary lymph node status, oestrogen and progesterone receptor status). The total median observation period was 4.8 years (3-9.1 years). Determination of the proliferation index proved to be the most important prognostic factor both for premenopausal and postmenopausal, nodal negative and nodal positive primary tumours when assessing the total survival time and the time that remains free from recurrences. A simultaneous assessment of low proliferation index and positive hormone receptor as a so-called low-risk situation shows in comparison to a high-risk situation (high proliferation index, negative receptor status) the most pronounced differences. For premenopausal women (younger than 50 years of age) the hormone receptor status has no prognostic significance as far as our group of patients is concerned, whereas for women of 50 years of age or older the receptor status is of great prognostic relevance. Besides the lymph node status, the proliferation index shows in a Cox regression model the greatest prognostic importance for the further course of a primary carcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Prognostic value of Ki-67 expression in localized cutaneous malignant melanoma.

BACKGROUND: The proliferative activity of some tumors is related to the development of metastatic disease and survival. Thus it could be used as a potential prognostic variable. OBJECTIVE: The purpose of this study was to determine the prognostic value of the Ki-67 index and of a "proliferation-based prognostic index" (PBPI, derived as tumor thickness x Ki-67 index/100) in localized cutaneous malignant melanoma (CMM). METHODS: The Ki-67 index (percent of total tumor nuclei) was determined in a series of 84 localized CMMs, with the use of the alkaline phosphatase-antialkaline phosphatase labeling method in formalin-fixed, paraffin-embedded material, and was correlated with other prognostic variables. Survival analysis was performed to determine whether the Ki-67 index and the PBPI could be predictive of metastatic spread or recurrent disease. A stratified analysis of these two parameters according to the tumor thickness was done. RESULTS: An association among the Ki-67 index and location, Clark level, tumor thickness and stage, and prognostic index was detected. Increased Ki-67 index and PBPI were associated with poorer overall survival (P =.03 and P <.0001, respectively) and disease-free survival (P =.01 and P <.0001, respectively). However, after stratification for thickness, only the PBPI showed independent prognostic significance, restricted to tumors thicker than 4 mm (P =. 03). CONCLUSION: The determination of the PBPI in CMM conveys prognostic information for localized thick (>4 mm) CMM, identifying two groups of patients with distinct outcome.

Biomarkers↗

Prognostic factors for perceived pain and function at one-year follow-up in primary care patients with neck pain.

PURPOSE: To identify prognostic factors for perceived pain and function with focus at one-year follow-up in primary care patients treated for non-specific neck pain. METHODS: A prospective study was performed including 193 neck pain patients. Before and after treatment period, and 12 months after the start date for treatment, patients completed a questionnaire including background data and aspects of pain, function and general health. Linear multiple regression analysis was used to identify prognostic factors with the dependent variables Oswestry score and pain intensity at 12-month follow-up. Response rate 81%. RESULTS: At 12-month follow-up, Oswestry score identified four prognostic factors: pain intensity; well-being; expectations of treatment; and duration of current episode. Adjusted R2 for the model was 0.32, and 20% of the patients had three of the four prognostic factors at entry, indicating risk of poor outcome. The dependent variable pain intensity revealed three prognostic factors: Oswestry score; duration of current episode; and similar problem during the previous five years. Adjusted R2 was 0.24, and 60% of the patients had two of the three prognostic factors at entry, indicating risk of poor outcome. CONCLUSIONS: Different prognostic factors (with the exception of duration of current episode) were identified by the two outcome variables. Thus the results suggest that it should be taken into account whether an impairment or disability outcome is used.

Adult↗

Prognosis and breast cancer. Recognition of lethal and favorable prognostic types.

Assignment of breast cancer patients to specific prognostic groups has been a relatively empty exercise until the recent acceptance of the effectiveness of systemic chemotherapy. The previous question of who should be so treated has changed in North America to a question of who should not be so treated. The availability of intensive chemotherapy for the worst prognostic groups as well as efficacious, low-toxicity adjuvant chemotherapy has made prognostication mandatory. The current major question is which women with breast cancer will not benefit from chemotherapy. We are actually much better at prognostication than many studies and the current broad search for new prognostic markers would indicate. The assignment of excellent prognosis categories by defined special histologic types or grade of breast cancer as well as other measures recognize women with survival approaching or equaling the general population. Likewise, extremely poor prognosis may be recognized in 20% to 40% of women with breast cancer by the presence of extensive mitoses or high proliferation index (by any modality) and poor differentiation (highest grade). Combined tumor size and nodal status data with high-grade indicates that women with these indicators will die within 2 to 3 years with as high as 80% certainty. The surgical pathologist still determines if cancer is present and must also determine if the tumor is in situ or invasive, its type or grade if invasive, and the extent of in situ component. Considering the diminution in overall size of cancers detected by modern techniques, it is clear that validation of newer prognostic variables will be more useful and will allow more separate determinations if adapted to tissue sections rather than tissue homogenates. The many measures of these carcinomas, such as size and nodal status, make multiparametric assessment of putative prognostic markers mandatory.

Biomarkers, Tumor↗

Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma.

OBJECTIVE: The authors sought to identify prognostic factors in the management of extremity soft tissue sarcoma. SUMMARY BACKGROUND DATA: The surgical management of soft tissue sarcoma has evolved because of advances in therapy, resulting in increased limb preservation and quality of life. However, identifying a subset of patients most likely to benefit from adjuvant chemotherapy has been difficult to achieve. METHODS: A retrospective analysis of a prospective data base of 182 patients with extremity sarcomas from 1970 to 1992 was performed. RESULTS: A histologic diagnosis of Ewing's sarcoma, synovial sarcoma, and angiosarcoma was associated with a 13-fold increased risk of death compared with liposarcoma, fibrosarcoma, and malignant peripheral nerve sheath histologic types after having adjusted for the other prognostic factors (p < 0.001). In addition to histologic type, high-grade sarcomas (p = 0.018), sarcomas greater than 10 cm in size (p = 0.006), and age at diagnosis (p = 0.016) were found to be important prognostic factors for survival but not for local recurrence. For the first time to their knowledge, the authors showed that mean mitotic activity has prognostic value after having adjusted for other prognostic factors, such as grade (p = 0.005). The only prognostic factors predictive for local recurrence were whether the patient presented with locally recurrent disease (p = 0.0001) or had microscopically positive margins (p = 0.052). CONCLUSIONS: The use of mitotic activity along with grade, size, histologic type, and age at diagnosis is prognostic for survival in extremity soft tissue sarcoma. The use of an objective pathologic feature, such as mean mitotic activity, is also useful in selecting patients for future systemic neoadjuvant or adjuvant trials and primary therapy.

Adolescent↗

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗

Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements.

OBJECTIVE: To evaluate the prognostic significance for AIDS occurrence of plasma levels of immune activation markers in comparison with and in conjunction with HIV viral load and CD4 T-cell measurements. DESIGN: A retrospective analysis was conducted of three plasma activation markers, the soluble tumor necrosis factor (TNF) receptor II (TNF-RII), neopterin and soluble interleukin-2 receptor levels, and of CD4 T-cell levels and plasma HIV viral load. SUBJECTS: The participants were 659 men taking part in the University of California Los Angeles Multicenter AIDS Cohort Study who were HIV-seropositive but AIDS-free in 1985. MAIN OUTCOME MEASURE: Clinically defined AIDS within 3 years. Failure time statistical regression models for the time to development of AIDS were used to assess prognostic capacity of the parameters alone and in combination. RESULTS: All the markers had prognostic capability. The levels of the three plasma activation markers correlated well with each other (median r = 0.61). They related less well with HIV RNA plasma levels (median r = 0.50) and least well with CD4 cell levels (median r = 0.36). Furthermore, plasma marker levels were shown to be able to stratify patients for prognosis within all the major categories of CD4 T-cell and HIV RNA levels. CONCLUSIONS: Plasma levels of soluble TNF-RII and other soluble markers of immune activation have prognostic capabilities which are different from HIV and CD4 T-cell levels. Combination of a single plasma activation marker measurement (such as soluble TNF-RII) with CD4 T-cell levels improved the prognostic capability of each. A new graphic technique for presenting prognostic capability indicated that plasma soluble TNF-RII and CD4 cell levels are better prognostic factors than HIV plasma level with CD4 cells < 200 x 10(6)/l. Inexpensive tests for one of the plasma activation markers, such as soluble TNF-RII or neopterin, can be useful for evaluations of HIV disease course, especially when expensive equipment, technical expertise and funding required for flow cytometry and for HIV load measurements are not readily available.

Antigens, CD↗

Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer.

OBJECTIVES/HYPOTHESIS: The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author's treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. STUDY DESIGN: Retrospective. METHODS: In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. RESULTS: The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. CONCLUSION: The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author's clinical experience and critical retrospective analysis, that the author's hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

Adult↗

Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis.

With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful. Tissue microarrays were constructed with triplicate cores (0.6 mm diameter) from the invasive margins of a consecutive single-institution series of 184 colorectal carcinomas. Immunostaining for p53, p21, p27, Ecadherin, and beta-catenin was scored. Tumor cell proliferation was assessed by mitotic indices and Ki-67 labeling, apoptosis by quantification of apoptotic bodies. Reduced nuclear immunostaining for p21 (<10%) and p27 (< or =50%) and reduced membranous expression of Ecadherin were significantly associated with a poorer clinical course by univariate analysis. beta-catenin immunostaining had no prognostic impact. Mitotic and apoptotic indices as well as Ki-67 labeling below the median were indicators of poor prognosis. Complete absence of p53 nuclear staining was a significant adverse prognostic factor. By Cox regression, p53 = 0%, p53 = 0%, in combination with p27 < or = 50%, the mitotic index and the combined mitotic and apoptotic index added prognostic information to UICC stage. The authors found that growth pattern, lymphohistiocytic response, lymphatic permeation, and venous spread, too, each was a strong prognosticator in addition to UICC stage. The results support that tissue microarrays are a useful tool for screening immunohistochemical markers for prognostic use. An immunopanel of p21, p27, and p53 could be useful for prognostication in colorectal carcinoma in addition to UICC stage.

Adult↗

Lymph node-based prognostics: limitations with individualized cancer treatment.

OBJECTIVES: Clinicians will commonly individualize adjuvant cancer therapy, on the basis of the number of involved lymph nodes and other clinicopathological factors, under the assumption that despite the expected statistical variability of such data one can nonetheless garner useful information for the individual case. Here the scientific basis of this assumption will be examined. METHODS: Survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for 19,107 breast, 4,234 gastric, and 4,058 rectal cancers were studied with Kaplan-Meier estimates and Cox proportionate hazard models. The minimal sample size required to discriminate between high and low-risk groups was determined from the hazard ratios between various comparative groups, and their respective frequencies. RESULTS: The number of involved nodes was the strongest prognostic factor for all 3 cancers, followed by tumor diameter and grade. Discrimination between high and low-risk nodal prognostic groups required samples of 30 to 200 cases, depending on the prognostics used and the specific tumor, to attain a two-sided alpha of 0.05% with 90% power. At the individual level such prognostications therefore were uninformative. CONCLUSIONS: Clinicopathological prognostics based upon the number of involved lymph nodes are subject to population heterogeneity that limits their application to large samples. At the individual level, these prognostics appear more spurious than useful. The use of such prognostics to tailor cancer treatment to individuals should be considered a specious practice; instead a more categorical approach, based on the results of randomized trials, should be used.

Breast Neoplasms↗

Reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder.

PURPOSE: We assessed the reproducibility and prognostic variability of grade and lamina propria invasion in stages Ta, T1 urothelial carcinoma of the bladder. MATERIALS AND METHODS: A total of 130 consecutive stages Ta, T1 urothelial carcinomas routinely diagnosed by 15 pathologists (original diagnosis) were reviewed by 3 independent experienced pathologists using 1999 WHO criteria (diagnoses 1 to 3 and reviewer consensus diagnosis). Interreviewer disagreement cases were blindly reviewed again. Each remaining disagreement case was discussed in a multihead microscope session to attempt to solve remaining disagreements. In cases of continuing disagreement the majority diagnosis on stage and grade was considered the consensus diagnosis. Stage progression at followup was the dependent variable. Stage progression-free Kaplan-Meier survival curves and hazard ratios of each stage and grade diagnosis were calculated and prognostic variability was determined. RESULTS: There was complete interobserver agreement on stage and grade among reviewers in 80% and 59% of cases, while it was 87.7% and 75.4%, respectively, after the second review. More than 1 grade difference occurred in 1.5% of cases (0% after the second review). The consensus and original diagnoses agreed on stage and grade in 68.5% and 62.3% of cases, respectively. Assignment of individual cases to 1 category of the 1999 WHO classification per reviewer varied considerably. The incidence of cases classified as stage T1 grade 3 by the reviewers was between 12.3% and 18.9% (average 14.1%). Consensus diagnosis grade had the strongest prognostic value (HR 68.8, range 8.9 to 528.0). Of the 63 original diagnoses of stage T1 tumors the consensus diagnosis down staged 35 (55.6%) to Ta and up staged 8 (12.7%) to T2-3. Progression was more common in the 20 consensus diagnosis stage T1 cases (5 or 25%) than in the 55 original diagnosis stage T1 cases (11 or 20%). Original diagnosis stage T1 tumors that were down staged by the consensus diagnosis showed less progression than consensus diagnosis confirmed stage T1 tumors (17% versus 25%). The prognostically worst subgroup (T1 grade 3) also showed considerable prognostic variation among reviewers (28% to 76% at 5 years of followup), in that the consensus diagnosis again had the highest prognostic significance (HR 3.5, range 1.2 to 10.2). At the end of the study all pathologists expressed that they were regularly uncertain about stage and grade assessment in an individual case in a considerable percent of all cases. CONCLUSIONS: Observer prognostic variability in staging and grading is considerable with potentially strong implications for patients. Interobserver variation did not decrease using the new 1999 WHO grading classification.

Carcinoma, Transitional Cell↗

Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V trial.

The significance of serum thymidine kinase (STK) as a prognostic indicator for patients with myeloma has been evaluated by determining the pre-treatment level of STK in a retrospective study of 547 patients from the Medical Research Council (MRC) V Myeloma Trial. Overall, STK was a highly significant prognostic factor (Chi 2 = 7.91; P = 0.005). At the time of censor, 23.4% of patients with a presentation STK of < 6 U/l but only 7.9% of the patients with an STK of > 11 U/l were still alive. STK proved to be a highly significant prognostic indicator for the 270 melphalan-treated patients (Chi 2 = 12.37; P = 0.0004) but had no prognostic significance for the 277 ABCM (adriamycin, BCNU, cyclophosphamide and melphalan) treated patients (Chi 2 = 0.29; P = 0.59). When the STK data was stratified for serum B-2-microglobulin (SB2M) it was demonstrated that STK was independent of SB2M and provided additional prognostic information for patients who were treated with melphalan. Thus patients with both a low STK and SB2M had the best prognosis (median survival 1677 d) and those patients with a high STK and SB2M had the worst prognosis (median survival 519 d). STK is a good prognostic marker for patients treated with melphalan but the prognostic significance of STK may disappear with the introduction of new chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Microvessel density compared with the Chalkley count in a prognostic study of angiogenesis in breast cancer patients.

AIMS: Evaluation of angiogenesis by intratumoral vessel profiles can be performed by different methods. The aim of this study was to investigate the prognostic value of estimates obtained by the intratumoral microvessel density (MVD) method and then to compare with corresponding estimates obtained by the Chalkley method. METHODS AND RESULTS: A total of 330 patients treated for primary, unilateral, invasive breast carcinoma were included. The median follow-up time was 14 years and 4 months. The microvessels were immunohistochemically stained by antibodies to CD34. MVD was not significantly correlated with any clinicopathological variables. By univariate analysis, MVD showed no prognostic value with regard to recurrence-free survival (RFS) or overall survival (OS), while the Chalkley count had significant prognostic value (P < 0.0001; RFS and OS). In the Cox multivariate analysis, MVD had no prognostic impact [median HR [confidence interval (CI)] was 0.93 [0.66, 1.32] for RFS; and HR [CI] was 0.86 [0.62, 1.19] for OS], while the Chalkley count [median HR (CI) was 2.12 (1.48, 3.06) for RFS; and HR (CI) was 1.71 (1.23, 2.37) for OS] provided independent prognostic value when adjusted for age, menopausal status, axillary lymph node status, tumour size, histological grade, adjuvant systemic treatment and radiation therapy. In comparing the results obtained by MVD in our study with those from other published studies we find good agreement. CONCLUSIONS: The Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.

Age Distribution↗

Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome.

BACKGROUND: The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L(-1) have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated. OBJECTIVE: To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death. DESIGN: Retrospective analysis. SUBJECTS AND METHODS: A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut-offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes. RESULTS: Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indicator for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90-0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51-0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59-0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75-0.90), sensitivity of 62% (CI = 46-76%), specificity of 93% (CI = 83-98%) at cut-off activity of > or =80 U L(-1). CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86-0.98), 0.91 (CI = 0.81-0.96), 0.93 (CI = 0.85-0.98), and 0.87 (CI = 0.76-0.94), respectively. CONCLUSIONS: Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.

Adult↗

A survival regression analysis of prognostic factors in colorectal cancer.

BACKGROUND: Many prognostic factors of colorectal cancer are known but their actual clinical validity is still uncertain. The aim of the present study was to verify, on the basis of our experience, the prognostic validy of variables for survival by using survival regression analysis. METHODS: From January 1978 to December 1986 the prognostic factors for 192 patients were analysed. These patients had undergone surgical resection for colorectal cancer. The follow up was completed in every patient by the end of December 1992, with a median follow up of 10 years (range 6-14 years). The prognostic factors considered in the statistical analysis were age, sex, size of tumour, site, grade, direct spread, node involvement and stage (according to Astler-Coller and pTNM). RESULTS: Of the prognostic factors, sex was the only one not to show any prognostic significance. In the survival regression analysis we have used an accelerated failure time model (equivalent to the Cox proportional hazard model); age, grade and stage were significant covariables. CONCLUSIONS: Although clinical pathological staging (pTNM) appears as a pre-eminent prognostic factor, and as our analysis shows, it needs a further variable (grading), which has been shown to affect the prognosis in a significant way.

Adult↗

Evaluation of prognostic factors following flow-cytometric DNA analysis after cytokeratin labelling: II. Cervical and endometrial cancer.

In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S-phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA-ploidy nor S-phase fraction were relevant prognostic parameters. But CV of the G(0)G(1)-peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA-aneuploidy (DNA-index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence-free survival. Especially DNA-aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA-ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA-ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA-parameters was found.

Adenocarcinoma↗

Early-stage melanoma: staging criteria and prognostic modeling.

Accurate risk assessment is central to the process of making rational surgical and systemic treatment recommendations for melanoma patients and in establishing appropriate clinical trial stratification criteria. The current American Joint Commission on Cancer melanoma staging system incorporated relevant prognostic variables to provide a framework for the estimation of risk for recurrence; however, significant prognostic heterogeneity exists within the stage groupings. In the stage I/II group, survival rates range from 40% to 95% as defined by the combination of tumor thickness and ulceration. The use of novel prognostic factors, such as mitotic rate, sentinel node biopsy, and prognostic modeling using a variety of factors, can minimize this prognostic heterogeneity and provide a more accurate and individualized prognostic profile. Recent modifications in the stage III criteria include the number of positive nodes, whether the nodal disease is microscopic or clinically apparent, and the presence of an ulcerated primary. Through these factors, survival estimates can be provided, but like the stage I/II group, wide ranges in prognosis exist. The complexion of the stage III population is in evolution as a result of increasing numbers of patients being diagnosed as having microscopic sentinel node disease. Contemporary efforts are focused on defining the prognosis and natural history of this group. Through prognostic modeling using the number of nodes involved, ulceration status, and a measure of disease burden--disease in the sentinel node--relatively homogeneous subgroups can be identified. Long-term follow-up of patients staged with PCR molecular techniques on sentinel nodes shows conflicting value in assessing prognosis and therefore cannot be routinely used outside a clinical trial. The combination of genomic profiling using microarray analyses and the development of targeted therapy holds the future promise of individualizing prognosis and therapy.

Humans↗