Significant Indicator Of Prognosis Research Articles

The clinical implication and translational research of OSCC differentiation.

The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO. OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

Manual and Semi-Automated Measurement and Calculation of Osteosarcoma Treatment Effect Using Whole Slide Image and Qupath.

In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath. In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage. Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment.

Mealtime challenges in patients with chronic obstructive pulmonary disease: Who is responsible?

To explore experiences of, and practices related to, mealtime challenges in patients with chronic obstructive pulmonary disease (COPD). Nutritional status is a significant indicator of prognosis and outcome in patients with COPD. Preventing unintended weight loss and helping patients regain weight are important nursing tasks. Dietary supplements have been effective in treating underweight in cases of stable COPD. However, compliance with long-term interventions is quite low. Improving nutritional intake through knowledge of meal-related challenges is the key to making further progress in preventing unintended weight loss. This study employed an ethnographic design using the go-along method. From September 2018-June 2019, 34hr of meal-related observations and informal conversations with purposefully selected patients (n=15) were completed at a Danish respiratory medicine ward and in patients' homes. We analysed the empirical data using a Ricoeur-inspired method. Reporting adheres to the COREQ Checklist. In this study, we identified the absence of professional responsibility as a main challenge. Mealtimes appeared to be relegated to a matter of nutrition, and common practices surrounding mealtimes were no longer observed. Patients became dependent individuals who had to settle for the food available. In addition, physiological challenges often resulted in patients re-evaluating the benefits of eating, concluding that it was not worth the effort and therefore not eating. Furthermore, patients were hesitant to communicate their needs, which left a number of nonverbalised challenges unattended. Overall, meal-related challenges pose a risk of unintended weight loss, and the health professionals' work with mealtimes lacks a coordinated, systematic approach. Further research is needed to develop or implement interventions that can accommodate mealtimes. This study contributes valuable knowledge that can be used to improve the quality of nursing care and prevent unintended weight loss in patients with COPD.

Detection of right ventricular myocardial fibrosis using quantitative CT attenuation of the right ventricular myocardium in the late phase on 320 slice CT in subjects with pulmonary hypertension

PurposeRight ventricular myocardial (RVM) fibrosis may be a significant indicator of prognosis in pulmonary hypertension (PH). To detect the presence of RVM fibrosis in PH subjects, we employed ECG gated 320-slice CT. Methods62 confirmed PH subjects (16 males; 55±16years; 45 chronic thromboembolic PH (CTEPH) who underwent conventional non-surgical medical therapy; and 17 pulmonary arterial hypertension (PAH)) underwent ECG-gated 320-slice CT. On CT, RV fibrosis was defined as contrast defect in the early phase and conversely abnormal enhancement in the late phase. ResultsRVM fibrosis was observed in 14 subjects (23%) on CT (CTEPH 22%; PAH 29%; P=0.91). CT attenuation of RVM in the late phase was significantly greater in subjects with RVM fibrosis than in those without (P=0.025). ROC curves of CT attenuation of RVM in the early and late phase, and ratio of CT attenuation of RVM in the early phase/late phase showed AUCs of 0.55, 0.70, and 0.65, respectively. The best cutoff points of 79.5 HU (sensitivity of 50% and specificity of 69% for CT attenuation of RVM in the early phase, P=0.59), 99.5 HU (sensitivity of 50% and specificity of 88% for CT attenuation of RVM in the late phase, P=0.025), and 1.416 (sensitivity of 29% and specificity of 94% for ratio of CT attenuation of RVM in the early phase/late phase, P=0.092) were used to distinguish subjects±RVM fibrosis. ConclusionQuantitative-measurement of CT attenuation of RVM in the late phase may be able to detect presence of RVM fibrosis in PH subjects.

Impact of Vascular Invasion of a Primary Tumor as a Strong Risk Factor for Disease Recurrence in Patients with Node-Positive Breast Cancer

The presence of lymph node metastasis is considered to be the most significant indicator of prognosis. However, in some cases with node-positive breast cancer, cancer cell dissemination is localized to the lymphatic systems. It is, therefore, important to develop selection criteria for strong adjuvant therapy in patients with node-positive breast cancer. This study was undertaken to evaluate the presence of vascular invasion that may reflect systemic disease as a predictor of disease recurrence in node-positive breast cancer. We retrospectively evaluated the cases of 134 consecutive female patients with breast cancer with lymph node metastasis who underwent radical breast operations. We examined the relationship between recurrence and clinicopathological factors, particularly vascular invasion. The presence of vascular invasion was found to be significant in a univariate analysis. The presence of vascular invasion was the independent risk factor in a multivariate analysis. Among the 66 patients without vascular invasion, four (6.1%) had disease recurrence. On the other hand, among the 68 patients with vascular invasion, 15 (22.1%) had a recurrence. It is interesting to note that despite the presence of lymph node metastasis, the group without vascular invasion had few patients with distant metastases. Our results suggest that the presence of vascular invasion could be an indicator of high biological aggressiveness and may be a strong prognostic factor for node-positive breast cancer.

Circulating Inflammatory and Hemostatic Biomarkers are Associated with All-Cause Death and Cancer Death in a Population of Community-Dwelling Japanese: the Tanushimaru Study.

BACKGROUNDIn patients with cardiovascular diseases, inflammatory and hemostatic biomarkers are significant indicators of prognosis. We investigated whether circulating inflammatory and hemostatic biomarkers were predictive markers for all-cause death and cancer death in a population of community-dwelling Japanese.METHODSWe studied 1,920 healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of inflammatory diseases and malignancy on a baseline questionnaire were excluded. Inflammatory and hemostatic biomarkers were measured in the remaining 1,862 participants, who were followed up periodically for 10 years. Multivariate proportional hazards regression analysis was used to estimate all-cause and cancer mortality.RESULTSA total of 258 participants died during follow-up: 87 from cancer, 38 from cerebro-cardiovascular diseases, and 133 from other diseases. Mean C-reactive protein (CRP) levels at baseline were significantly higher in decedents than in survivors. Mean von Willebrand factor (vWF) levels at baseline were significantly higher in decedents than in survivors. The Cox proportional hazards model after adjustments for age and sex showed that CRP (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.06–1.51) and vWF (HR, 1.01; 95% CI, 1.00–1.01) were independent predictors of all-cause death. CRP (HR, 1.40; 95% CI, 1.06–1.86) and vWF (HR, 1.01; 95% CI, 1.00–1.02) were also independent predictive markers for cancer death.CONCLUSIONSSerum CRP and vWF were predictors of all-cause death and cancer death in the population of community dwelling Japanese.

Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma

The treatment of bone metastasis in association with thyroid cancer represents a difficult challenge. Given the paucity of patients with bone metastasis and the difficulty of treating this disease, few studies have investigated the clinical features and prognostic factors of bone metastasis from differentiated thyroid cancer. During the 31-year-period from 1976 to 2006, a total of 1,398 patients underwent initial thyroidectomy at Cancer Institute Hospital for differentiated thyroid carcinomas, including standard papillary thyroid carcinoma, papillary microcarcinoma (primary tumor diameter < or =1.0 cm), and follicular thyroid carcinoma. Among these, 25 (2%) patients displayed bone metastasis at initial presentation (synchronous) and 27 patients showed bone metastasis during follow-up (metachronous). The records for these 52 patients were reviewed retrospectively to identify prognostic factors and analyze treatment strategies. Univariate analysis for disease-specific survival indicated metachronous bone metastasis and the presence of distant metastasis at sites other than bone as indicators of significantly worse prognosis. The type of cancer (papillary thyroid carcinoma versus follicular thyroid carcinoma) was not a significant indicator of prognosis; however, patients with papillary microcarcinoma showed significantly worse survival than patients with standard papillary and follicular thyroid carcinoma. A significant survival advantage was observed among patients who underwent radioactive iodine therapy, and better prognosis seemed to be obtained with greater doses of radioactive iodine. Operative resection of metastatic bone lesions also seemed to be associated with better prognosis. A multivariate analysis for disease-specific survival identified the coexistence of distant metastasis at sites other than bone as the only independent variable indicative of poor prognosis. In the absence of definitive, effective treatments for this disease, radioactive iodine therapy combined with resection of bone metastasis, wherever possible, seems to represent the most potent therapy available. Although bone metastasis is a strong sign of poor prognosis, early detection and administration of appropriate therapy using radioactive iodine seems likely to improve the survival rate and quality of life in patients with bone metastasis from differentiated thyroid carcinoma.

Summary Health Status Measures in Advanced Heart Failure: Relationship to Clinical Variables and Outcome

Background Patient-centered health status measures are important because they capture the patient's perspective on their heart failure, but it is unclear which of these have independent prognostic significance. Methods and Results A total of 142 consecutive subjects from a specialty heart failure clinic were assessed at baseline with a broad array of clinical, laboratory, and self-report measures including four summary measures of health status. The relationships between these measures and their association with the combined end point of transplantation or death over a mean follow-up of 3 years were examined. In unadjusted analyses, the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score had the strongest association with the combined end point (HR [for each unit score difference] = 0.98 [0.96–0.99], P = .002). In the adjusted Cox proportional hazards model including all 4 summary measures, the Seattle Heart Failure Score, V0 2, systolic blood pressure, and medical comorbidity, only the Standard Gamble utility remained significantly associated with time to the combined end point (HR [for each 0.01 utility score difference] = 0.98 [0.97–0.99], P = .007). Conclusions Our study suggests that summary health status measures are simple and significant indicators of prognosis in advanced heart failure patients. The KCCQ summary score summarizes a wide range of clinical variables from the patient's point of view, whereas the standard gamble utility contains important prognostic information not captured in usual clinical variables.

Phenotype of Peripheral Blood Leukocytes and Survival of Patients with Metastatic Colorectal Cancer

Immune dysfunction is prevalent in metastatic cancer. Few patients with colorectal cancer metastases are cured, and among the strategies aimed at improving the therapeutic results in patients with metastatic colorectal cancer, immunotherapy is being increasingly investigated. We evaluated retrospectively the prognostic significance of peripheral blood leukocytes in 59 patients with metastatic colorectal cancer. The relative numbers of CD3+, CD3+CD4+, CD3+CD8+, NK (CD3-CD16+CD56+), CD3+DR+, CD3+CD25+, CD3+CD69+, CD19+, CD19+CD23+, CD8+CD28+, CD8-CD28+, CD8+CD57+, CD14+DR+ and CD14+CD16+ leukocytes were analyzed by two-color flow cytometry. A three-step approach was adopted to identify predictors of prognosis using regression analysis. Based on the results of univariate survival analysis, the absolute number of white blood cells, NK/CD3+CD69+ and NK/white cell count ratios were significant indicators of prognosis. In the multivariate regression analysis a model was obtained using a single parameter, the NK/CD3+CD69+ ratio, predicting the survival with 10-15% power of regression. The present results indicate that the NK/CD3+CD69+ ratio in peripheral blood may be an independent variable in a regression model predicting the overall survival of patients with colorectal cancer metastases to be tested in prospective studies.

Phenotype of peripheral blood leukocytes and survival of patients with metastatic colorectal cancer

Immune dysfunction is prevalent in metastatic cancer. Few patients with colorectal cancer metastases are cured, and among the strategies aimed at improving the therapeutic results in patients with metastatic colorectal cancer, immunotherapy is being increasingly investigated. We evaluated retrospectively the prognostic significance of peripheral blood leukocytes in 59 patients with metastatic colorectal cancer. The relative numbers of CD3+, CD3+CD4+, CD3+CD8+, NK (CD3_CD16+CD56+), CD3+DR+, CD3+CD25+, CD3+CD69+, CD19+, CD19+CD23+, CD8+CD28+, CD8_CD28+, CD8+CD57+, CD14+DR+ and CD14+CD16+ leukocytes were analyzed by two-color flow cytometry. A three-step approach was adopted to identify predictors of prognosis using regression analysis. Based on the results of univariate survival analysis, the absolute number of white blood cells, NK/CD3+CD69+ and NK/white cell count ratios were significant indicators of prognosis. In the multivariate regression analysis a model was obtained using a single parameter, the NK/CD3+CD69+ ratio, predicting the survival with 10-15% power of regression. The present results indicate that the NK/CD3+CD69+ ratio in peripheral blood may be an independent variable in a regression model predicting the overall survival of patients with colorectal cancer metastases to be tested in prospective studies. (Int J Biol Markers 2005; 20: 126-33).

Nodular sclerosing Hodgkin disease: new grading predicts prognosis in intermediate and advanced stages

AbstractThe prognostic value of histologic classification and single histomorphologic parameters in Hodgkin disease has been widely debated in the literature. Whereas several former studies identified single parameters to be of clinical relevance, some recent reports have doubted the prognostic value of histology using modern treatment. Grading of the largest histologic category of Hodgkin disease, nodular sclerosis (NS), has been controversially discussed concerning clinical relevance. In this study, 965 cases of NS were reviewed to assess 9 histomorphologic parameters. The histologic results were correlated with laboratory and clinical findings and with overall survival and disease-free survival. Based on these results, a new grading of the NS category was established. The new grading, based on the 3 criteria eosinophilia, lymphocyte depletion, and atypia of the Hodgkin/Reed-Sternberg cells, was a significant indicator of prognosis in intermediate and advanced stages. Patients investigated in this study represent an outstanding collection because all of them were enrolled in the prospective multicenter clinical trial of the German Hodgkin Lymphoma Study Group. All of them had been staged uniformly according to the Ann Arbor system and had received stage-adapted modern treatment according to multimodality protocols. A subtle analysis of histology could represent a possible way to identify patients with a significantly better or worse prognosis. This new grading should help to avoid overtreatment to reduce severe therapy-related side effects such as acute toxicity and chronic sequelae such as cardiopulmonary complications and secondary neoplasias.

Neutral endopeptidase/CD10 andAminopeptidase N/CD13 gene expression as a prognostic factor in non-small cell lung cancer

Neutral endopeptidase modulates the growth of lung cancer, while aminopeptidase N degrades the extracellular matrix and is involved in cell motility. We studied the metastasis mechanism to detect novel metastasis-associated molecules and to evaluate them for clinical application. We studied the relationship between the expression of neutral endopeptidase and aminopeptidase N by quantitative reverse transcript-polymerase chain reaction analysis in 132 patients with non-small cell lung cancer undergoing radical surgery from 1991 to 1996. Patients with neutral endopeptidase-positive and aminopeptidase N-negative tumors were defined as group A, those with neutral endopeptidase-positive and aminopeptidase N-positive or neutral endopeptidase-negative and aminopeptidase N-negative tumors as group B, and those with neutral endopeptidase-negative and aminopeptidase N-positive tumors as group C. The 5-year survival of group A patients (92.9%) was significantly better than that of group B patients (64.7%) and much better than that of group C patients (38.2%) (P = 0.0011). Neutral endopeptidase and aminopeptidase N thus have statistically significant P in overall survival in Cox regression (P = 0.019). Neutral endopeptidase and aminopeptidase N gene expressions are significant indicators of prognosis.

Cyclin-dependent kinase inhibitor p27Kip1 expression and interaction with other cell cycle-associated proteins in mammary carcinoma.

p27, cyclin D1, and retinoblastoma (Rb) protein have been demonstrated using immunohistochemistry in 189 cases of primary breast carcinoma with long-term follow-up. There was a statistically significant association between the expression of p27 and both cyclin D1 and the retinoblastoma gene product (pRb), corresponding to their close interactions in regulating the G1/S transition in the cell cycle. Low levels of p27 were seen in high-grade, rapidly proliferating, oestrogen receptor-negative tumours. In univariate analysis, low p27 expression was associated with a reduced relapse-free and overall survival. In multivariate analysis, p27 was not an independent predictor of survival when either histological grade or proliferative activity (S-phase fraction) was included in the model. When the combined expression of p27 and cyclin D1 was related to survival, patients with high levels of p27, regardless of their cyclin D1 status, did well, whilst those with low p27 had a poor outcome. The only exception, in the latter group, was patients with tumours expressing high levels of cyclin D1, who did as well as the high p27 group. We have shown that in clinical material p27 expression is associated with proliferative activity and while univariate analysis shows it to be a significant indicator of prognosis, this significance is lost in multivariate analysis when traditional prognostic factors are included in the model. The interest in p27 expression in mammary carcinoma lies in its behaviour when examined in combination with other G1 cell cycle regulators.

Carcinoma of the breast in males: a multiinstitutional survey.

Breast carcinoma in males is infrequent, and information regarding the results of modern treatment is limited. Cases of breast carcinoma in males were accrued from multiple hospitals in one region to determine treatment, survival, and prognostic factors. A retrospective review was performed of 217 cases of breast carcinoma in males accessioned at tumor registries of 18 health care institutions in eastern Wisconsin between 1953 and 1995. Of the 217 cases, 215 (99.1%) were carcinomas. The majority of carcinomas were of invasive ductal type and presented as masses. Carcinoma in situ accounted for 5.5% of cases. The 5- and 10-year observed survivals for men were 50.6% and 23.7%, respectively. A high rate of post-treatment mortality from comorbid disease was found. Stage, axillary lymph node status, number of lymph nodes with metastases, and tumor hormone receptors were significant indicators of prognosis. Adjuvant systemic chemotherapy and hormone therapy improved the prognosis of patients with axillary lymph node metastases and hormone receptor positive tumors. Earlier stage at presentation and improved 5-year survival were found in cases occurring between 1986-1995 compared with those occurring in earlier years. Use of modified radical mastectomy and systemic adjuvant therapy also increased since 1986. The clinical, pathologic, and prognostic features of breast carcinoma in men are similar to those reported for women. The poorer prognosis of men is related to older age at diagnosis, more advanced stage of disease at presentation, and high mortality from comorbid disease. Earlier diagnosis, less radical surgery, and use of systemic adjuvant therapy are coincident with an improved prognosis for men.

Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis.

To identify clinical and histologic prognostic factors and to investigate whether immunohistochemical detection of p53 expression might contain prognostic information, a retrospective study of patient and tumor characteristics was performed in 225 cases of papillary and follicular thyroid carcinomas. The analyses were based on cause-specific and crude survival. In univariate analysis, age at diagnosis, tumor size, presence of distant metastases, histology (papillary contra follicular type), extrathyroidal invasion, necrosis in primary tumor, and p53 expression were significant prognostic indicators. For 211 patients (96%) all information was available and Cox's proportional hazard model was applied. The authors found that age, distant metastases, necrosis in primary tumor, extrathyroidal invasion, and p53 expression were significant prognostic factors. Analyses of cause-specific and crude survival gave similar results. The authors conclude that age at diagnosis, presence of distant metastases, necrosis in primary tumor, and extrathyroidal invasion are important prognostic factors, and that immunohistochemical detection of p53 protein in the primary tumor is a significant and independent prognostic indicator, which might be of value in the treatment planning in patients with papillary or follicular thyroid carcinomas.

Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas.

To evaluate angiogenesis as a prognostic marker of transitional cell carcinoma of the bladder and to assess its relationship to established variables for survival. Forty-five tumours (two G2T2, seven G3T2 and 36 G3T3) from 36 men and nine women with a mean age of 73 years (range 50-91), who had been followed-up for a median of 37 months (range 1-50), were examined. Vessels were immunohistochemically highlighted using an antibody to the platelet endothelial cell adhesion molecule, CD31. Microvessel density was quantified using a Chalkley point eyepiece graticule. Univariate analysis of survival showed stage, grade and vascular count were significant indicators of prognosis (P = 0.002, P = 0.007, P = 0.019 respectively). No relationship was observed between stage and grade and vascular count. In a Cox proportional hazard model, adjusted for age and stage, microvessel density not only remained a significant prognostic indicator (P = 0.026) but was as informative as stage in predicting overall survival. A high vascular count conferred a 2.5 increased risk of mortality. These findings suggest that assessment of angiogenesis by microvessel quantification is an independent predictor of survival in patients with invasive bladder carcinoma and might be useful in selecting those who would benefit from adjuvant therapy.

From dukes through jass: Pathological prognostic indicators in rectal cancer

In the recently described Jass staging system for resected adenocarcinoma of the rectum, peritumoral lymphocytic infiltration and tumor growth pattern are introduced as significant indicators of prognosis in conjunction with depth of tumor invasion and lymph node metastasis. The authors of this study have tested the applicability of the Jass system by reviewing 348 resected rectal cancers for 12 pathological variables, including two newly recognized features, namely the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat. By univariate analysis improved 5-year survival rate was associated with tubular-type adenocarcinoma, low tumor grade, retention of tubule configuration and nuclear polarity, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of extramural vein invasion by tumor, all levels of intramural and extramural invasion short of widespread local tumor dissemination, a Crohn's-like lymphoid reaction pattern, and absence of both nodal metastasis and tumor nodules in perirectal fat. By Cox stepwise proportional hazards analysis, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and extramural venous invasion retained independent prognostic significance. Peritumoral lymphocytic infiltration and tumor growth pattern of the Jass staging system failed to compete successfully with other variables in the proportional hazards model, in part because of their correlation with the model's selected variables. Both intramural and extramural extent of tumor invasion coupled with lymph node metastasis form the cornerstones of rectal cancer staging. However, other factors do refine prognostication. From this study the Crohn's-like lymphoid reaction emerges as a significant new independent indicator of prognosis for survival from rectal cancer. Although the Crohn's-like lymphoid reaction and extramural vein invasion took precedence as staging variables in this study, a complex interrelationship with other parameters was observed.

Tumor Cell Lines Established in Vitro: An Independent Prognostic Factor for Survival in Non-Small-Cell Lung Cancer

To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung cancer. Cohort study. Single-institution tertiary care center. One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. Tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%). Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P less than 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P less than 0.0001 for curable group; P less than 0.01 for palliative group). In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.

Acute critical ischaemia of the limb: A prospective evaluation

A total of 119 patients with acute peripheral arterial ischaemia were studied prospectively to validate the definition of acute critical ischaemia suggested by the working party of the International Vascular Symposium. The majority of the patients had primary treatment using thrombolytic therapy. Overall limb salvage after 30 days was achieved in 56% of the patients, 19% required amputations and 25% died. Comparisons of the outcome in patients with or without a distal neurosensory deficit (limb salvage 30% vs. 72%, P = 0.0001) and those with absent or audible Doppler ankle blood flow (limb salvage 37% vs. 78%, P = 0.0001) confirmed that the severity of the initial ischaemia was a significant indicator of prognosis. The definition of acute critical ischaemia as assessed by objective measurement of Doppler pressures has been validated and can be used to divide patients into groups with critical and sub-critical ischaemia with different prognoses.