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DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact.

The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA index (DI) was determined by flow cytometry in adjacent sections from the same paraffin-embedded specimens. The correlation between tumor thickness and nuclear nu v was only moderate (r = .60). Euploid lesions had a smaller nuclear nu v than aneuploid tumors (2p = .01), but with considerable overlap. No significant association between tumor thickness and DI could be demonstrated. Single-factor analysis showed prognostic value of nuclear nu v and tumor thickness (2p = .0007 and 2p = .03, respectively), whereas DI was without prognostic impact (2p = .54). When analyzing the three parameters in a Cox model, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas.

Adult↗

The prognostic value of PSA levels in radiation therapy of patients with carcinoma of the prostate: the UCLA experience 1988-1992.

BACKGROUND AND OBJECTIVES: Pretreatment prostate-specific antigen (PSA) levels may be of prognostic significance for patients with prostate cancer. Posttreatment PSA data are more limited. This study was undertaken to examine the prognostic role of pretreatment and posttreatment PSA levels in the radiation treatment of patients with carcinoma of the prostate. METHODS: One hundred one patients who received primary radiation therapy at UCLA between 1988 and 1992 for clinical stage A to D1 prostate cancer were analyzed. Included were 4 patients with stage A, 77 with stage B, 16 with stage C, and 4 with stage D. All patients had pretherapy and posttherapy PSA values. Patients received definitive radiation therapy with photons (81), neutrons (13), or interstitial implant (7). Correlations were made with other prognostic factors and treatment outcome. RESULTS: Median follow-up was 28 months. At last follow-up, 64% were without evidence of disease, 17% had rising PSA profiles or failure of PSA to normalize (chemical failure), and 19% had local recurrence and/or distant metastases. The 4-year overall survival was 85%, whereas actuarial survival free of chemical or clinical failure was only 32%. Pretreatment PSA levels and posttreatment PSA level normalization at 6 months correlated significantly with disease-free survival. On univariate analysis, pretreatment PSA levels correlated significantly with stage, high versus low Gleason score, and outcome. Posttreatment PSA level normalization at 6 and 12 months correlated with stage, pretreatment PSA level, and outcome, but not with Gleason score. Only PSA level normalization at 6 months and age were independent variables using multivariate analysis. PSA nadir values differed significantly between patients free of disease and those who failed. CONCLUSIONS: In our analysis, posttreatment PSA levels were independently predictive of outcome, whereas pretreatment PSA levels, while correlating with other prognostic factors, were not independently predictive. Given the prognostic value of posttreatment PSA levels, it is appropriate that chemical failures be included in outcome analyses, although this will lower disease-free survival.

Adenocarcinoma↗

The prognostic significance of steroid receptor activity in tumor tissues of patients with primary breast cancer.

The prognostic significance of steroid-receptor activity is still debatable. Discrepancies in results are probably attributable to few patients, heterogeneous patient populations, and short follow-up. We investigated the prognostic significance of estrogen- and progesterone-receptor (ER and PgR, respectively) activity as a continuous variable in a homogeneous patient population. The prognostic significance of steroid-receptor activity was examined in 329 node-negative and 320 node-positive unselected breast cancer patients. In node-negative patients, ER values of primary tumors between 100 and 400 fmol/mg protein appeared to be a significant predictor for low risk of recurrence, whereas high ER (> 400) revealed an unfavorable prognosis. The classic cutoff level of ER (< 10 fmol/mg proteins) had no prognostic significance, however. In patients receiving adjuvant chemotherapy--the node-positive breast cancer patients--the classic cutoff value of ER (10 fmol/mg protein) predicts significantly distant metastases-free survival and overall survival only in the first 4 years of follow-up after diagnosis. Progesterone receptor is a time-dependent prognosticator in node-negative breast cancer patients (cutoff point for PgR, 80 fmol/mg). In node-positive breast cancer patients treated with chemotherapy or a combination of chemo- and hormonal therapy, PgR values lower than 60 fmol/mg had a worse prognosis. The results show the poor performance of standard cutoff points for ER and PgR positivity in predicting prognosis. Better prognosis is related to higher receptor levels but this relation is predominantly time-dependent. Moreover, patients who have high ER levels have a prognosis that is worse when compared with intermediate ER levels. Standard cutoff points for steroid receptors should not be used to select patients for prognosis.

Adult↗

Prognostic factors after conservative surgery and radiation therapy for early stage breast cancer.

A retrospective review was conducted of all early-stage breast cancer patients treated with breast-conservation surgery plus radiation therapy (BCS/RT) to determine mortality and recurrence rates and to evaluate prognostic factors for these outcomes. Between 1982 and 1988, 121 patients with stages I and II breast cancer were treated with BCS/RT at our institution. Most of the patients (83%) had re-excision of the initial biopsy site and at final surgical evaluation, only 4 patients had positive margins (3.2%). Median follow-up was 89.7 months. Cox proportional hazards regression models were used to select prognostic factors significant for breast cancer-specific mortality, overall disease recurrence, and local recurrence. Breast cancer survival rates were 92% at 5 years and 83% at 10 years. Prognostic factors predicting breast cancer mortality included positive lymph nodes (relative risk=.9; 95% confidence interval, 1.2,12.2) and a higher grade (relative risk=1.9; 95% confidence interval, 1.1,3.3). For disease recurrence, prognostic factors included positive nodes (relative risk=2.6; 95% confidence interval, 1.2, 5.5), and a negative progesterone-receptor status (relative risk=0.3; 95% confidence interval, 0.2, 0.8). Local recurrence rates were 2.5% at 5 years and 14% at 10 years. No prognostic factors were significant for local recurrence; however, most patients had negative margins after surgery.

Adult↗

Prognostic factors for local control in non-small-cell lung cancer treated with definitive radiation therapy.

Radiotherapy plays an important role as a treatment for locally advanced non-small-cell lung cancer (NSCLC), but local failure still occurs in 70% to 80% of the patients. A retrospective analysis was carried out to evaluate the local control predictors for non-SCLC. From January 1990 to December 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. The significance of prognostic variables on local control was evaluated using univariate analysis and Cox stepwise regression model. The prognostic index was calculated according to the value of each prognostic factor on local control. Median local progression-free survival time of the whole group was 9.7 months, and 1-, 3-, and 5-year actuarial local progression-free survival were 54%, 24%, and 19%, respectively. Univariate and multivariate analyses showed patients with smaller tumor volume, earlier clinical staging, and treated with higher total dose in shortened overall treatment time had better local control. Tumor volume, clinical staging, and radiotherapy methods were independent prognostic factors on local control. The prognostic index model could predict the local control condition of NSCLC treated with radiation therapy more effectively than a single variable such as TNM staging.

Adult↗

Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories.

The cyclin-dependent kinase inhibitor p27KIP1 has been proposed as a valuable prognostic indicator for a variety of human neoplasms. Immunohistochemical reactivity for p27KIP1 and the proliferation marker Ki67/Mib1 were investigated in 90 thyroid carcinomas of follicular cell origin. The neoplasms were divided into three prognostic groups on the basis of their morphologic features: group 1, well-differentiated papillary or follicular carcinomas with favorable pathologic features (43 papillary carcinomas and 4 minimally invasive follicular carcinomas); group 2, papillary or follicular carcinomas with unfavorable pathologic features (21 poorly differentiated carcinomas and 2 papillary carcinomas, tall cell variant); and group 3, undifferentiated, or anaplastic, carcinomas. p27KIP1 expression (p = 0.007) and Ki67/Mib1 labeling index (p = 0.02) showed a strong correlation with the subdivision of the thyroid carcinomas in the three prognostic groups with a significant linear trend for tumors with low p27KIP1 (p = 0.002) and high Ki67/Mib1 labeling index (p = 0.005) to segregate into the unfavorable categories (groups 2 and 3). Low p27KIP1 expression, but not cellular proliferation, was related to adverse prognostic factors, such as large tumor size (p = 0.03) and extrathyroidal extension (p = 0.01), but the correlation was not independent of the subdivision in the three groups. Low p27KIP1 expression (p = 0.03) and high proliferative rate (p = 0.02) were associated with poor survival, reflecting the close association between patient morbidity and mortality rates and tumor differentiation. No significant association could be seen between p27KIP1 or cellular proliferation and clinicopathologic parameters (e.g., age, sex, tumor size, extrathyroidal extension, vascular invasion, lymph node metastases, distant metastases, tumor stage, and survival rate) within any of the groups, or the histologic diagnosis of papillary versus follicular carcinoma irrespective of their degree of differentiation. Modulation of p27KIP1 and cellular proliferation patterns in thyroid carcinoma correlate with tumor differentiation and support the morphologic classification of thyroid carcinoma into prognostically relevant categories.

Adenocarcinoma, Follicular↗

Prognostic significance of the histopathologic recognition of low- and high-grade components in stage I-II B-cell gastric lymphomas.

The prognostic value of histopathologic features was assessed in 83 patients with stage I-II gastric B-cell lymphomas (PGL). The following histotypes were considered: low-grade mucosa-associated lymphoid tissue (MALT)-type lymphoma (LGML; n = 35), diffuse large B-cell lymphoma with areas of MALT-type lymphoma (DLCLML; n = 20) and diffuse large B-cell lymphoma without areas of MALT-type lymphoma (DLCL; n = 28). Low-grade (LG) and high-grade (HG) components, lymphoepithelial lesions (LEL), size of cells giving rise to LEL, and amount and growth pattern of large cells (LC) were analyzed. Five-year cause-specific survival (CSS) for patients with LGML, DLCLML, and DLCL were 94%, 84%, and 64%, respectively (p = 0.05). LG component or LEL were associated with a significantly longer 5-year CSS, whereas the presence of an HG component, defined as clustered LC greater than 10% of neoplastic population, was significantly related to a shorter survival. Lymphomas with LC disposed in clusters were associated with a worse survival in comparison with cases with scattered LC. The presence of scattered LC 5%-10% appeared irrelevant in LGML. When analysis was limited to DLCLML/ DLCL patients, the presence of LG component or LEL was associated with a significantly longer 5-year CSS, whereas the existence of LEL formed by LC (HG LEL) did not modify survival. Multivariate analysis, adjusted by the main prognostic factors, confirmed the independent and significant association between histopathologic categorization and survival. Age, stage, lactate dehydrogenase (LDH) ratio, thrombocytopenia, and use of chemotherapy had independent prognostic value. In conclusion, histopathologic categorization is an independent prognosticator in PGL. The formation of compact clusters by LC, rather than their amount, is a true prognostic variable. The presence of scattered LC 5%-10% appears irrelevant in LGML. LG component and LEL are favorable predictors in HG lymphomas, helping to identify two subsets of DLCL with different prognosis.

Adolescent↗

Thin level IV malignant melanoma. A subset in which level is the major prognostic indicator.

A small proportion of "thin" malignant melanomas will metastasize and cause death. To assess the role of discordance between the major indicators of tumor depth (thickness and level) as a possible explanation for this phenomenon, prognosis by level has been examined in 255 cases, with tumors ranging in thickness from 0.6 to 1.1 mm. This is the range of thickness at which levels II, III, and IV overlap. The 5-year survival rate of patients with level IV tumors in this thickness range (59.35%) was poor (p less than 0.0001), relative to that of patients with level II (96.8%) and III (94.49%) lesions in the same range of tumor thickness. The distributions of other major prognostic indicators, among the groups of patients with tumors at each level, were examined to assess the possible contribution of factors other than level to the differences in survival between the three groups. These differences in survival could not be attributed to differing distributions of tumor thickness, tumor location, or patient sex. Of six prognostic variables, examined by Cox multivariate regression analysis, for tumors of thickness 0.6 to 1.1 mm, only level was found to have independent prognostic significance (p = 0.0025). The thin level IV melanoma appears to be an important exception to the rule that this melanomas are associated with an excellent prognosis. In this, as well as in other studies, after accounting for the effect on prognosis of tumor thickness, level has been shown to be a prognostic indicator with independent significance. The continued use of level as a prognostic indicator, in addition to thickness, is recommended.

Female↗

Surgical management and prognostic factors in patients with subungual melanoma.

OBJECTIVE: Forty-six cases of subungual melanoma were reviewed to identify significant clinicopathologic prognostic factors, determine the role of DNA content analysis in the biologic assessment of these tumors, and evaluate the effectiveness of amputation level, lymph node dissection (LND), and regional limb perfusion on the survival of these patients. BACKGROUND: Subungual melanoma is a unique and rare subtype of melanoma, constituting only 1% to 3% of cases. Thus, little is known about prognostic factors and optimal management of patients with this disease. Moreover, the appropriate level of amputation and LND and limb perfusion in the management of subungual melanoma remain controversial. METHODS: Forty-six patients underwent amputation alone or in combination with LND and/or regional limb perfusion for primary subungual melanoma. The effects of these treatment modalities and the prognostic significance of patient and tumor-related variables, including DNA flow cytometric data, on overall survival were assessed. RESULTS: Univariate statistical analysis identified six factors that significantly affected patient survival. They were stage at diagnosis (p = 0.0001), percentage of aneuploid cells (p = 0.01), presence of ulceration (p = 0.02) or bone invasion (p = 0.02), thickness of the primary lesion (p = 0.03), and percentage of cells in S-phase (p = 0.03). Multivariate analyses identified tumor stage and S-phase fraction as independent prognostic factors in these patients. Survival did not differ among patients who received amputation alone or those who underwent amputation in combination with LND or perfusion (p = 0.90); however, the use of limb perfusion reduced the incidence of locally recurrent disease. The level of amputation did not affect patient survival (p = 0.74) or the incidence of local recurrence. CONCLUSIONS: The study identified several significant prognostic factors, including DNA flow cytometric parameters, in patients with subungual melanoma. In addition, it showed that conservative amputation of the affected digit at the level of the proximal interphalangeal or metacarpophalangeal/metatarsophalangeal joint appears to be safe, provided that clear margins are obtained. Although isolated limb perfusion may reduce the incidence of local recurrence, LND, or limb perfusion in the routine management of subungual melanoma remains controversial.

Adult↗

Prognostic factors after cryotherapy for hepatic metastases from colorectal cancer.

OBJECTIVE: To establish the prognostic importance of different patient and tumor characteristics in cryotherapy for liver metastases from colorectal cancer. SUMMARY BACKGROUND DATA: Hepatic cryotherapy has been used as a treatment of nonresectable liver metastases from colorectal cancer in almost 1000 patients worldwide, and its safety and efficacy are well established. However, tumor eventually recurs in most patients and they die of their disease. The knowledge of prognostic factors would allow the selection of patients who are more likely to benefit from this treatment and patients who may need additional treatment. METHODS: Between April 1990 and May 1997, 195 patients were treated with hepatic cryotherapy. Out of this group, the authors identified 116 patients with colorectal cancer who received cryotherapy for ablation of liver metastases. Survival was estimated with the Kaplan-Meier method, using the log-rank test for univariate analysis for significance of possible prognostic factors. For multivariate analysis, a Cox regression was used. RESULTS: One patient (0.9%) died of postoperative myocardial infarction. The total perioperative morbidity rate was 27.6%. Median survival and the 5-year survival rate were 26 months and 13.4%. The following factors were identified as independently associated with a favorable outcome: low presurgical serum level of carcinoembryonic antigen (CEA), small (< or =3 cm) diameter of cryoablated metastases, absence of untreated extrahepatic disease at laparotomy, absence of nodal involvement at primary resection, complete cryotreatment, synchronous development of liver metastases, and good or moderate differentiation of the primary tumor. Although univariate analysis suggested a favorable prognosis in patients who did not receive blood transfusion during surgery and patients younger than 51 years, this was not confirmed in multivariate analysis. In addition, normalization of the serum CEA level after treatment was an important prognostic marker in the subgroup of patients with elevated serum CEA levels before surgery. CONCLUSIONS: Hepatic cryotherapy is a safe and effective treatment option for patients with nonresectable liver metastases from colorectal cancer, with promising results regarding survival. The prognostic factors established in this series may allow better patient selection to improve the outcome in suitable patients.

Aged↗

Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study.

OBJECTIVE: In 1986 a prospective multicenter observation trial in patients with resected gastric cancer was initiated in Germany. An analysis of prognostic factors based on the 10-year survival data is now presented. PATIENTS AND METHODS: A total of 1654 patients treated for gastric cancer between 1986 and 1989 at 19 centers in Germany and Austria were included. The resected specimen were evaluated histopathologically according to a standardized protocol. The extent of lymphadenectomy was classified after surgery based on the number of removed lymph nodes on histopathologic assessment (25 or fewer removed nodes, D1 or standard lymphadenectomy; >25 removed nodes, D2 or extended lymphadenectomy). Endpoint of the study was death. Follow-up is complete for 97% of the included patients (median follow-up of the surviving patients is 8.4 years). Prognostic factors were assessed by multivariate analysis. RESULTS: A complete macroscopic and microscopic tumor resection (R0 resection according to the UICC 1997) could be achieved in 1182 of the 1654 patients (71.5%). The calculated 10-year survival rate in the entire patient population was 26.3% +/- 4.7%; it was 36.1% +/- 1.6% after an R0 resection. In the total patient population there was an independent prognostic effect of the ratio between invaded and removed lymph nodes, the residual tumor (R) category, the pT category, the presence of postsurgical complications, and the presence of distant metastases. Multivariate analysis in the subgroup of patients who had a UICC R0 resection confirmed the nodal status, the pT category, and the presence of postsurgical complications as the major independent prognostic factors. The extent of lymph node dissection had a significant and independent effect on the 10-year survival rate in patients with stage II tumors. This effect was present in the subgroups with (pT2N1) and without (pT3N0) lymph node metastases on standard histopathologic assessment. The beneficial effect of extended lymph node dissection for stage II tumors persisted when patients with insufficient lymph node dissection (<15 nodes) were excluded from the analysis. There was no difference in the postsurgical morbidity and mortality rates between patients with standard and extended lymph node dissection. CONCLUSIONS: Lymph node ratio and lymph node status are the most important prognostic factors in patients with resected gastric cancer. In experienced centers, extended lymph node dissection does not increase the mortality or morbidity rate of resection for gastric cancer but markedly improves long-term survival in patients with stage II tumors. This effect appears to be independent of the phenomenon of stage migration.

Adult↗

Multivisceral resection for locally advanced primary colon and rectal cancer: an analysis of prognostic factors in 201 patients.

OBJECTIVE: To review a single-center experience with 201 multivisceral resections for primary colorectal cancer to determine the accuracy of intraoperative prediction of potential curability, to identify prognostic factors, and to examine the effect of surgical experience on immediate outcome and long-term results. SUMMARY BACKGROUND DATA: Locally advanced colorectal cancer may require an intraoperative decision for en bloc resection of surrounding organs or structures to achieve complete tumor removal. This decision must weigh the risk of complications and death of multivisceral resection against a potential survival benefit. Little is known about prognostic factors and the influence of surgical experience on the outcome of multivisceral resection for colorectal cancer. METHODS: Patients undergoing multivisceral resection for primary colon or rectal cancer between 1982 and 1998 were identified from a prospective database. Patients were followed up according to a standard protocol. RESULTS: Multivisceral resection was performed in 201 of 2,712 patients with a median age of 64 years. Postoperative rates of complications and death in 201 patients were 33% and 7.5%, respectively. A potentially curative resection was possible in 130 of 201 patients (65%) and histologic tumor infiltration was shown in 44% of patients with curative resection. Intraoperative assessment of curability was unreliable. After curative resection, the local recurrence rate was 11% and the overall 5-year survival rate was 51%. Multivariate analysis identified intraoperative blood loss (relative risk 1.7-6.4, P <.001), age 64 years or older (RR 3.7; P <.001), and UICC stage as independent prognostic factors (RR 2.0; P =.009). No prognostic significance was found for histologic tumor infiltration, the number of resected organs, or surgical experience. CONCLUSIONS: Multivisceral resection is safe, and long-term survival after curative resection is similar to that after standard resection. Because palliative resections cannot be predicted accurately at the time of surgery, every effort should be made to achieve complete tumor resection. Major blood loss but not surgical experience per se is an independent prognostic factor.

Aged↗

Local failure and prognostic factors in ductal carcinoma in situ: concentration on recent publications.

PURPOSE OF REVIEW: Traditional therapy for ductal carcinoma in situ has been mastectomy or conservative surgery plus radiation, but interest in more expeditious therapies such as conservative surgery alone is growing. A first step in considering changes in an already successful treatment is to evaluate tumor and patient factors that may predict outcome. Identifying and understanding these prognostic factors will aid researchers in designing new treatment paradigms. The purpose of this review is to assess the value of commonly accepted potential prognostic factors in patients with ductal carcinoma in situ. RECENT FINDINGS: During this past year several retrospective studies have evaluated putative prognostic factors in ductal carcinoma in situ. We will compare these later publications with results from prospective randomized trials and one meta-analysis. SUMMARY: There does not appear to be unanimous agreement on the prognostic factors associated with increased risk of local failure in patients treated with conservative surgery and radiation for ductal carcinoma in situ. In our chosen papers, however, comedonecrosis and positive margins are most likely prognostic factors for increased local failure.

Adult↗

Prognostic significance of tumor cell morphometry, histopathology, and clinical parameters in advanced ovarian carcinoma.

The prognostic value of clinicopathologic data and tumor cell morphometry was assessed in 49 consecutive patients with advanced epithelial ovarian carcinoma (Stage III-IV as defined by the International Federation of Gynaecologists and Obstetricians [FIGO]). Single-variant analysis proved that nuclear area at the 10th, 50th, and 90th percentiles and nuclear density were the strongest prognostic factors. To assess difference in prognostic influence between morphometric and clinicopathologic factors, Cox regression analysis was carried out and revealed nuclear density and age as prognostically significant (p less than 0.0003 and p less than 0.0004, respectively). Choice of chemotherapy, FIGO stage, histologic grade, and mitotic activity index (MAI) were not of additional prognostic importance. Objective measurement of morphometric factors is simple, highly reproducible, and adequate for routine work and promises to be of clinical value in therapeutic decision-making in advanced ovarian carcinoma.

Adult↗

The prognostic value of nuclear versus architectural grading in endometrial adenocarcinoma: a Gynecologic Oncology Group study.

The pathologic grade of endometrial adenocarcinoma is widely recognized as an important prognostic and therapeutic indicator. However, disagreement persists about the optimal method of determining grade. The pathology committee of the Gynecologic Oncology Group employs a system based on the proportion of tumor in glandular array; this system is both reproducible and predictive of outcome. Others have suggested that grading based on nuclear pleomorphism and the size of nucleoli provides better prognostication. We compared the three-level architectural grading system (AG) with a two-level nuclear grading system (NG) to determine reproducibility and prognostic value in 88 cases of stage 1 endometrial adenocarcinoma. Three pathologists made independent assessments of grade by each method. The division of tumors by architectural arrangement was superior for predicting survival (83%, 73%, and 44%, AG, p = 0.005; vs. 79% and 61%, NG, p = 0.14) and equivalent to nuclear grading for prediction of recurrence. Both systems were moderately reproducible (k = 0.49, AG; k = 0.57, NG). Assessment of NG was more tedious than that of AG. Subdivision of architectural grade based on high nuclear atypia, as recommended in current, International Federation of Gynecology and Obstetrics guidelines, did not improve prognostication. Because grading based on nuclear pleomorphism does not provide prognostic information superior to that resulting from architectural grading, we do not advocate its use in routine surgical pathology practice.

Adenocarcinoma↗

The use of a modified Delphi procedure for the determination of 26 prognostic factors in the sub-acute stage of stroke.

The aim of this study was to reach consensus about the prognostic factors when deciding the discharge destination from a hospital stroke unit, and to construct a prognostic conceptual framework. To realise an optimal integration of knowledge from research findings and from clinical experience by expert opinions we used a 'modified Delphi Technique', which is the most commonly used method for the production of clinical guidelines. The process yielded 26 prognostic factors, which were arranged in clinical and social sub-domains. The sub-domains and the factors within each sub-domain were prioritised according to their assumed predictive value for the decision process. The order of importance of the prognostic factors in the clinical domain was: (1) disabilities, (2) pre-morbid disabilities, (3) impairments and (4) disease/biology; and the order of importance of the factors in the social domain was: (1) home front, (2) social situation and (3) residence. The Delphi procedure is an excellent instrument to determine and prioritise prognostic factors. With this procedure research-based and consensus-based knowledge can be combined. For a valid procedure it is mandatory to state explicitly in advance how the scores will be judged, and to explain the scientific level of the evidence during the whole procedure.

Activities of Daily Living↗

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↗

Prognostic value of tumour vascularity in primary melanoma.

To investigate the prognostic value of tumour vascularity we studied 84 patients with primary melanomas ranging in tumour thickness (Breslow) from 0.37 to 7 mm and in depth of tumour infiltration (Clark) from II to V. Vascularization was assessed by immunohistochemistry with a CD-31 antibody recognizing endothelial cells. The CD-31-positive vessels were counted and the degree of vascularization was correlated with the survival of the patients. In addition, the relationship between blood vessel density and some histopathological data is discussed. In our study, the multivariate Cox model showed that the only independent variable in disease-free survival was tumour thickness (Breslow classification) and the only one in overall survival was depth of tumour infiltration (Clark classification). In disease-free survival, tumour thickness (Breslow classification) was a clear prognostic factor (P = 0.004) after 4 years' follow-up, as were depth of tumour infiltration (Clark classification) (P = 0.04) and ulceration (P = 0.04). In overall survival, tumour vascularity was the strongest prognostic factor at 4 years, high vascularity being associated with a good prognosis (P = 0.06). Clark classification was also a prognostic factor (P = 0.02) in overall survival. We conclude that high vascularization is associated with a better prognosis but is not an independent prognostic indicator.

Adult↗