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Increased serum levels of basic fibroblast growth factor in lung cancer patients: relevance to response of therapy and prognosis.

Angiogenesis is controlled by inhibitors and angiogenic factors. Among these, basic fibroblast growth factor (bFGF) is closely involved in cancer proliferation and has been related to progression and prognosis of various cancers, including lung cancer. To evaluate the role of bFGF, we measured serum levels of bFGF from healthy controls (Ctrl) and 106 patients with lung cancer, including 31 adenocarcinomas (AD), 29 squamous cell carcinomas (SQ), and 46 small cell carcinomas (SCLC), by enzyme-linked immunosorbent assays. Moreover, we evaluated the relationship between serum levels of bFGF and clinical outcome. Serum levels of bFGF in AD, SQ, SCLC, and Ctrl were 7.6 (0.5-32.5) (median (range)), 7.4 (0.5-36.7), 7.1 (0.5-34.8) and 3.0 (1.5-6.0) pg/ml, respectively (P<0.05). Serum bFGF levels did not differ between clinical stages in non-small cell lung cancer (NSCLC; AD+SQ). In SCLC, we found a significant difference in serum levels of bFGF between chemotherapy (and/or radiotherapy) responders (complete response+partial response) and non-responders (no change+progressive disease) (9.2 (0.6-34.8), 4.4 (0.5-17.4) pg/ml, respectively (P=0.018)), whereas there was no difference in NSCLC. Moreover, serum bFGF levels in SCLC patients had significant impact in prognosis by uni and multivariate analysis (P=0.014, 0.018, respectively). We concluded that bFGF has an important role in the prognosis of patients with SCLC.

Adult↗

Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe.

BACKGROUND: Since the incidence of the histological subtypes of lung cancer in industrialised countries has changed dramatically over the last two decades, we reviewed trends in the incidence and prognosis in North America, Australia, New Zealand and Europe, according to period of diagnosis and birth cohort and summarized explanations for changes in mortality. METHODS: Review of the literature based on a computerised search (Medline database 1966-2000). RESULTS: Although the incidence of lung cancer has been decreasing since the 1970s/1980s among men in North America, Australia, New Zealand and north-western Europe, the age-adjusted rate continues to increase among women in these countries, and among both men and women in southern and eastern Europe. These trends followed changes in smoking behaviour. The proportion of adenocarcinoma has been increasing over time; the most likely explanation is the shift to low-tar filter cigarettes during the 1960s and 1970s. Despite improvement in both the diagnosis and treatment, the overall prognosis for patients with non-small-cell lung cancer hardly improved over time. In contrast, the introduction and improvement of chemotherapy since the 1970s gave rise to an improvement in - only short-term (<2 years) - survival for patients with small-cell lung cancer. CONCLUSIONS: The epidemic of lung cancer is not over yet, especially in southern and eastern Europe. Except for short-term survival of small cell tumours, the prognosis for patients with lung cancer has not improved significantly.

Adult↗

Prognosis of non-surgically treated, clinical stage I lung cancer patients in Japan.

OBJECTIVE: The optimal management of stage I lung cancer is surgical resection. However, some of these patients are not candidates for surgery because of several medical problems. We analyzed prognosis of non-surgically treated, clinical stage I lung cancer patients. METHODS AND RESULTS: There were 21211 lung cancer patients registered from 1982 to 1991 in the data-base of the Japanese National Chest Hospital Study Group for Lung Cancer, and the number of non-surgically treated, clinical stage I lung cancer patients during the 10 years was 802. The 5- and 10-year survival rates of the 799 patients, exclusive of two carcinoid tumors and one adenid cystic carcinoma which have good prognosis, were 16.6 and 7.4%. We analyzed the 799 patients according to several prognostic factors. Sex, T factor of the tumor, histology, performance status and the method in which lung cancer was detected were prognostic factors, but age and treatment method were not associated with prognosis. Forty-nine patients survived for 5 years or more without surgical resection, but the survival rate continued to decrease even after 5 years, and the 7- and 10- year survival rates were 34.4 and 18.1% in the 49 patients. CONCLUSIONS: It is a fact that there are long-term survivors in non-surgically treated, stage I lung cancer patients. However, the rate is low, and the survival curve continues to decrease even after 5 years. Long-term survivors might suggest the presence of a lung cancer in which the tumor growth is slow.

Adenocarcinoma↗

Gemcitabine and oxaliplatin: a safe and active regimen in poor prognosis advanced non-small cell lung cancer patients.

BACKGROUND AND AIMS: Most patients with non-small cell lung cancer (NSCLC) cannot tolerate a cisplatin-based chemotherapy because of old age, general conditions, and/or multiorgan metastatic sites. Oxaliplatin is active in NSCLC, offers advantage in terms of toxicity, and shows synergism with gemcitabine. The aims of this phase II study were to evaluate the response rate and toxicity of the gemcitabine-oxaliplatin combination in patients with advanced NSCLC and poor prognosis. METHODS: Patients were given a gemcitabine infusion (1000 mg/m(2) over 30 min on days 1 and 8) followed by oxaliplatin (65 mg/m(2) over 120 min on days 1 and 8) every 21 days for six cycles. RESULTS: Thirty-two patients with poor-prognosis advanced NSCLC received 136 cycles. There were 25 males and seven females, and the median age was 65 years (range 29-76). Fifty-six percent of patients had adenocarcinoma, and 31% had squamous cell carcinoma. Sixty-six percent of patients had stage IV disease, and 34% had stage IIIB disease. Eastern cooperative oncology group (ECOG) performance status was 2-3 in 50%, 1 in 44%, and 0 in 6% of patients. Eight patients (25%) had been previously treated with cisplatin or carboplatin. All patients were symptomatic. Of the 32 patients who received study drug, five (16%) achieved partial response, six (19%) had minor response, three (9%) had stable disease, and 15 (47%) progressed. The median overall survival was 27 weeks. Thirty-one patients were evaluable for toxicity: seven patients (23%) had grade 3-4 thrombocytopenia with no bleeding; four patients (13%) had grade 3-4 neutropenia with no febrile neutropenia, and three patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and six patients (19%) had grade 1-2 neurotoxicity. CONCLUSION: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.

Adult↗

Expression of caveolin-1 is associated with poor prognosis of patients with squamous cell carcinoma of the lung.

BACKGROUND: Caveolin-1, as a major component of caveolae, is involved in the regulation of cell cycle by impacting various signaling pathways. Previous studies of caveolin-1 in cancer showed two contrary results. In most in vitro studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the elevated expression of caveolin-1 was often reported to be associated with poor clinical outcome in human studies. These results indicate differential biological functions of caveolin-1 depending on the development and progression stage of cancer in vivo. METHODS: To clarify the correlation between the clinicopathologic profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1, 107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous cell carcinomas were immunohistochemically evaluated for the expression of caveolin-1 by the tissue-array method. RESULTS: Caveolin-1 was expressed in 34 cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The expression of caveolin-1 was statistically correlated with pathologic stage (stage I and II vs. III; P<0.001), pT (T1 and T2 vs. T3 and T4; P=0.001), and pN (N1 vs. N2 and N3; P=0.0143). The patients with caveolin-1 expression in pulmonary squamous cell carcinomas showed a poorer prognosis than those in caveolin-1-negative group (P=0.0345). CONCLUSION: The expression of caveolin-1 is significantly correlated with advanced pathologic stage and poor prognosis in pulmonary squamous cell carcinoma. The results of current study suggest that the expression level of caveolin-1 may be a candidate factor for predicting prognosis in patients with pulmonary squamous cell carcinoma.

Adult↗

Impact of abnormal uptakes in bone scan on the prognosis of patients with lung cancer.

The detection of bone metastases is important in the management of patients with lung cancer because bone metastasis has a major impact on the prognosis and choice of treatment modality. Bone scan has been widely used for early detection of bone metastases but its low specificity complicates confirmation of bone scan findings. To evaluate the effects of abnormal bone scan findings on the prognosis of patients with lung cancer, we retrospectively analyzed the effect of abnormal uptakes on the prognosis of patients with primary lung cancer. The overall survival of patients with abnormal bone uptake was not significantly different from those without abnormal uptake. However, the patients with more than two abnormal bone uptakes had significantly shorter survival than those with no abnormal uptake (P<0.05). To confirm the effect of abnormal bone uptakes on survival, we compared the survival curves of three patient groups without knowledge of bone scan findings: group A, stage I-IIIB with more than two abnormal bone uptakes (potential stage IV); group B, stage IIIB with no abnormal bone uptake (true stage IIIB); and group C, stage IV with no abnormal bone uptake. Group A revealed shorter survival than group B (P<0.05). But, there was no significant difference in survival times between group A and group C. In the Cox regression analysis, the presence of more than two abnormal bone uptakes was a significant prognostic factor (P=0.0277), together with performance status, stage, and albumin. These results suggest that one or two abnormal bone uptake at diagnosis did not affect overall survival of the patients, and that the patients with more than two abnormal bone uptakes are considered as clinical stage IV because of high probability of bone metastases.

Bone Neoplasms↗

[Two cases of polyarteritis nodosa with a good prognosis?].

INTRODUCTION: Polyarteritis nodosa is a systemic necrotizing vasculitis that may become serious, even with no usual poor prognosis factors. EXEGESIS: We report two cases of polyarteritis nodosa with negative histology, starting only with an extensive necrosis of the extremities. The treatment, associating corticosteroids and, secondarily, immunosuppressors, did not prevent a bilateral half-leg amputation for the two patients. In the first case the disease stabilized, but in the second one, it worsened, leading to death within 2 years. CONCLUSION: This clinical aspect of the disease is unusual and should be identified because of its bad prognosis. It might benefit from a treatment from the outset associating corticosteroids and immunosuppressors, even with no usual bad prognosis factors.

Adrenal Cortex Hormones↗

[The diabetic foot: prognosis in a series of 75 patients].

Prognosis for 75 diabetic patients with foot ulcers. The aim of the study was to evaluate the prognosis regarding amputation and mortality in 75 consecutively presenting diabetic patients admitted because of foot ulcers. Median follow-up was 16 months. The amputation rate was 69% but only 4 major amputations were done. The mortality rate was 10.6%. Peripheral vascular disease was present in 69 patients. These finding stress the poor short-term prognosis of diabetic patients with foot ulcers and peripheral vascular disease.

Adult↗

[Individualized prognosis in non-small-cell carcinoma. A multivariate approach].

With the aim of providing a system to give individualized initial prognosis for patients with non-small cell lung cancer (NSLC), we performed a multivariate discriminant analysis with combinations of various prognostic factors, studying 93 patients with diagnoses of stage II NSLC and complete followup information. All had undergone surgery at our hospital. Survival longer than or less than one year was defined as the dependent variable: independent variables more clinical, analytical, lung function, histological, anatomical and surgical data. Among the 31.2% of patients who died within one year, tumor size was noticeably greater (6.0 +/- 2.1 cm versus 4.8 +/- 2.0 cm; p = 0.11) and serum albumin was lower (3.7 +/- 0.7 g/dl versus 3.9 +/- 0.6 g/dl; p = 0.039); we found no significant differences among the remaining independent variables in the preliminary univariate analysis. The linear function obtained with discriminant analysis allowed us to classify the patients correctly in 87.1% of cases, with a diagnostic sensitivity of 79.3%, specificity of 90.6%, positive predictive value of 79.3% and negative predictive value of 90.6% for patients who died during the first year. The independent variables that were associated with poor prognosis were large tumor size, long duration of symptoms, low albumin level, high alkaline phosphate level, presence of 2 or more N1 affected nodes, pneumonectomy and presence of perioperative complications. Our findings allow us to conclude that the simultaneous analysis of a variety of prognostic factors can help to give an accurate prognosis for individual patients with the same anatomical stage classification.

Aged↗

[The influence of angina the week before a first myocardial infarction on short and medium-term prognosis].

INTRODUCTION AND OBJECTIVES: The implications of early angina on the prognosis of myocardial infarction are controversial. The aim of this study was to assess the effect of angina one week before the first myocardial infarction on short and medium-term prognosis. PATIENTS AND METHOD: A total of 290 consecutive patients (107 with previous angina and 183 without it) with the first myocardial infarction were studied to determine the effect of preceding angina on short and medium-term prognosis. Further criteria for inclusion were no previous history of angina > 1 week before the first myocardial infarction, and no evidence of prior structural cardiopathy. The end points studied were death and congestive heart failure in the acute phase of myocardial infarction and during the follow-up. RESULTS: Patients with a history of prodromal angina were less likely to experience in-hospital death, heart failure or combined end-point (3.7 vs 11.5%; 4.6 vs 15.8%; 7.5 vs 21.3%) (p = 0.002). There was also a difference between groups in the follow-up (4.1 vs 13.2%; p = 0.03). Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of death and heart failure in the acute phase of myocardial infarction as well as in the follow-up. CONCLUSIONS: The occurrence of angina one week before the first myocardial infarction protects against death and heart failure in the acute phase of myocardial infarction as well as in the medium follow-up.

Analysis of Variance↗

[The changing prognosis of myocardial infarction in the reperfusion era: implications for evaluation and management of ventricular arrhythmias].

The prognosis of patients with ischemic heart disease has improved markedly with the introduction of reperfusion therapy and with aggressive efforts to modify risk factors. Consequently, the rate of cardiovascular events after myocardial infarction has decreased to approximately 5% over a period of 2 years as compared with the 20% to 30% reported in the prethrombolytic era. In this context, it is unlikely that the results of previous studies in the prereperfusion era can be applied to this group of patients. Others have demonstrated that the identification of subgroups of patients at greater risk and the search for new risk markers can significantly improve survival of patients who are at high risk despite reperfusion therapy. For example, it was found in the GISSI-2 study that unsuitability for exercise stress testing was associated with a mortality of 7% at 6 months. Other factors that determine poor prognosis after myocardial infarction are transitory heart failure, left ventricular dysfunction, and advanced age. The active search for new risk markers has identified other factors such as nonresolution of ST-segment changes, impaired ventricular filling, anomalous baroreflex sensitivity, or T-wave alternans that may be of benefit in assessing risk. Also, the timing of risk stratification can be critical. Often, risk factors have been analyzed weeks or even months after infarction instead of before hospital discharge. Approximately 30% of patients have deterioration of left ventricular function in the next 2 or 3 months, whereas others have improvement, highlighting the difficulties in attempting to risk stratify at one point in time. Although nobody doubts the effect that coronary revascularization has had on the prognosis of ischemic heart disease or the effectiveness of aspirin, beta -blockers, lipid-lowering drugs, and angiotensin-converting enzyme inhibitors, the search for cardiac or noncardiac risk markers can contribute notably to increasing the survival of patients who have had myocardial infarction.

Arrhythmias, Cardiac↗

[Clinical prediction of the early prognosis in acute myocardial infarct].

Several clinical factors can influence the pathophysiology, clinical course and prognosis of acute myocardial by different means. Some of them may be easily detected through the history, physical examination or ECG in an early phase. The knowledge of these factors may help the therapeutic decision making of patients with myocardial infarction. The influence for the main clinical factors (age, sex, risk factors, cardiologic antecedents and evolutive findings) on the short-term prognosis of acute myocardial infarction is reviewed. An analysis of the likely mechanisms of the influence of these factors on infarct prognosis is also performed.

Age Factors↗

Influence of surgery and postoperative therapy and tumor characteristics on patient prognosis in advanced ovarian carcinomas.

OBJECTIVES: The prognosis in advanced ovarian cancer depends on clinical, morphological, biological and therapeutic variables. However, little is known about their real influences and interrelationships. STUDY DESIGN: One hundred and nineteen long-term, follow-up patients with advanced ovarian carcinoma were analyzed. Overall survival was related to the extent of debulking surgery, response to chemotherapy and several clinicomorphological, histopathological, and immunohistochemical variables. RESULTS: Among all variables, both radical surgery and response to chemotherapy exerted the greatest influence on patient prognosis as shown in both univariate and multifactorial analyses. Most established prognostic factors were of minor importance. Success of chemotherapy correlated with lower residual tumor volume, CA125 expression, FIGO-stage, and serous tumor type. CONCLUSION: Prognosis and chemotherapeutic success in advanced ovarian cancer seem to be interrelated and may be influenced by the intensity of surgical interventions. This demands for greatest cytoreduction during initial surgery and correction for residual tumor volume and success of therapy in studies of prognostic factors.

Antineoplastic Agents↗

Differentiation of mechanism and prognosis of traumatic brain stem lesions detected by magnetic resonance imaging in the acute stage.

We retrospectively evaluated the MRI from 17 patients with primary brain stem injury obtained in the acute stage. Clinical and radiological findings were analyzed in these 17 patients. T2-weighted imaging proved to be most sensitive and specific for the diagnosis of primary brain stem injury. We found two patterns of brain stem injury. The good prognosis group showed ventral brain stem lesions or dorsal superficial brain stem lesions. On the other hand the poor prognosis group showed deep dorsal brain stem lesions. These acute stage findings are seen only temporally in many cases so that it is most important to examine MRI findings in the acute stage to evaluate the prognosis of the patient. MRI was valuable in predicting the outcome. The possible mechanism of brain stem injury in patients with head injury is briefly discussed.

Acute Disease↗

B-cell lymphoma of 708 cases in Japan: incidence rates and clinical prognosis according to the REAL classification.

New insights into the pathogenesis of lymphoid malignancies have been gained through novel techniques such as genetic, molecular and immunologic methods. Recently, based on those findings, a new classification system for lymphoid malignancies, known as the REAL classification, has been proposed. To clarify the relation between the histological classification and prognosis of B-cell lymphoid malignancies, we re-classified 708 cases. In all cases, the B-cell phenotype and/or genotype was confirmed by immunohistochemical staining and/or receptor gene analysis. The most common B-cell lymphoma types were diffuse large B-cell lymphoma (58.8%), follicular lymphoma (12.1%), marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (9.0%) and mantle cell lymphoma (5.9%). Minor types were lymphoblastic lymphoma (3.4%), Burkitt's lymphoma (2.4%), nodal marginal zone lymphoma (2.1%), lymphoplasmacytic lymphoma (2.0%) and plasmacytoma (1.4%). Rare types were prolymphocytic lymphoma and splenic marginal zone lymphoma. Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (1) the low risk group consisted of follicular lymphoma, marginal zone lymphoma of MALT, nodal marginal zone lymphoma, plasmacytoma and lymphoplasmacytic lymphoma; (2) the intermediate risk group consisted of diffuse large B-cell lymphoma, Burkitt's lymphoma and mantle cell lymphoma; and (3) the high risk group consisted of lymphoblastic lymphoma. In MALT, the low grade type had a better prognosis than the high grade type. In diffuse large B-cell lymphoma, the common type had a better prognosis than the variant type, which mainly consisted of the immunoblastic lymphoma. The histological classification will have a benefit for the clinical approach.

Adolescent↗

The impact of nucleolar organizer regions for the lymph node spread and prognosis of invasive ductal mammary carcinoma.

In primary tumours of 40 patients with invasive ductal carcinomas the significance of nucleolar organizer regions (NORs) for metastatic spread to the axillary lymph nodes and for the prognosis was assessed. Silver-stained tissue sections were investigated by means of semiautomated image analysis. The nucleolar organizer regions of 100 tumour cell nuclei per specimen were measured. The number as well as the area of the NORs were evaluated together with morphometrical and DNA features, histopathological and clinical data. By means of multivariate discriminant analysis, significant differences between tumours of 20 node-negative and 20 node-positive patients could be found. The mean number of NORs was significantly higher in patients with lymph node metastases (p = 0.0059), whereas the mean area was significantly lower in node-positive patients. By using the NOR number as the only parameter both groups were classified with an overall efficiency of 95%. There was also a significant difference between long-term and short-term survivors by considering the mean number of NORs, but the Auer-type, the 2 cDl value, and the DNA-grade of malignancy were of better predictive value. Within the group of node-negative patients the NOR number was most suitable for distinguishing between good and poor prognosis, whereas within the group of node-positive patients once more the DNA parameters played the most decisive role for predicting prognosis. With regard to the small number of patients the results have to be considered as preliminary. Further investigations in a more extensive population are necessary.

Adult↗

Morphology of male breast carcinoma in the evaluation of prognosis.

We studied a series of 44 consecutive cases of male breast carcinoma over a 14 year period in order to evaluate the clinico-pathological characteristics and the impact of some morphologic factors on prognosis. The age of the patients ranged from 38 to 84 years (mean 62 +/- 10.8). All the patients presented a painless mass, associated with nipple retraction in 13 cases (29.4%), skin ulceration in 12 cases (27.2%) and nipple discharge in 6 (13.6%). Microscopically all the tumors were infiltrating ductal carcinomas, 42 being of the NOS type. A better survival was associated with low mitotic index, T 1 tumors and absence of peritumoral lymphatic permeation. However, only these two parameters had statistical significance and were found to have predictive value on the prognosis of the disease. The degree of differentiation assessed according to Bloom and Richardson's classification showed no influence on prognosis. Post surgical radiotherapy did not seem to influence the outcome of the disease.

Adult↗

[Sarcomas of the female genitalia: therapy and prognosis (author's transl)].

216 sarcomas of the female genitalia were treated at the University hospitals for women of Freiburg and Tübingen between the years 1957 to 1977. 76% originated from the uterine corpus; 28% (46/164) of the sarcomas of the corpus uteri were detected as incidental findings. The 5 year survival rates is 54% in stage I, 25% in stage II, and 40% in all stages (52/131). Postoperative irradiation of stage I cases of sarcomas of the corpus uteri diminished local recurrence but not metastases. Extirpation of the ovaries has no influence on local recurrence. Sarcomas of the vulva and cervix have a comparatively good prognosis, whereas the prognosis of the sarcoma of the ovary is very bad. The bad prognosis of sarcomas of the female genitalia points out the necessity of developing cooperative clinical trials on the effectiveness of adjuvant chemotherapy.

Female↗