DNA index by flow cytometric analysis: an additional prognostic factor in advanced ovarian carcinoma without residual disease after primary operation

Prediction of duration of a patient's stay in the ICU after cardiac surgery is difficult. In 652 consecutive adult patients undergoing elective coronary artery bypass graft (CABG) surgery, we analysed prospectively preoperative and immediate postoperative variables thought to influence duration of stay in the ICU. With univariate analysis, we found that age, preoperative left ventricular ejection fraction, bypass time, aortic cross-clamp time, blood transfusions and the number of inotropic agents administered in the immediate postoperative period (for at least 6 h) were significant correlates of duration of stay in the ICU. However, logistic regression analysis showed that the number of inotropes was the most important determinant of stay in the ICU, with an overall prediction accuracy of 94.8%. The main cause of prolonged stay in the ICU (more than 2 days) was low cardiac output syndrome. We conclude that analysis of perioperative variables enhanced our ability to accurately predict duration of stay in the ICU in cardiac surgery patients. The number of inotropic agents administered during the first 6 h after operation was the most important determinant of duration of stay in the ICU.     

The clinical relevance of static disease (no change) category for 6 months on endocrine therapy in patients with breast cancer

This study reports on the clinical relevance of the static disease (SD) category in 255 breast cancer patients on endocrine therapy. All patients had received first- and second-line endocrine therapy and were assessed for response by the International Union Against Cancer (UICC) criteria. We did not include patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy, e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, remained in long-term remission on first-line endocrine therapy. We analysed survival from initiation of first-line endocrine therapy by the remission criteria, i.e. complete response (CR), partial response (PR), static disease (SD) or progressive disease (PD), achieved on that therapy. Patients were divided into those with metastatic breast cancer (MBC) and non-metastatic disease. There was no significant difference in survival from starting first-line endocrine therapy between patients who obtained CR, PR or SD: all three groups of patients survived significantly longer than patients who showed PD within 6 months (all P < 0.0001 except CR versus PD [MBC] which was P < 0.002). Equally, for second-line endocrine therapy there was no difference in survival between patients who obtained CR, PR or SD: all three groups (CR, PR and SD) survived significantly longer than PD (all P < 0.0003 except for CR versus PD which was P < 0.003 for non-metastatic and P < 0.059 for MBC). Durable SD appears to be a clinically useful criteria of therapeutic remission.     

Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment

In 1981-1982 urinary albumin excretion rates were determined in 211 diabetic and 216 non-diabetic subjects aged 60-74 years. By April 1992 122 diabetic and 58 non-diabetic probands had died. Dividing the two study populations at an albumin excretion rate of 15 micrograms/min showed that 69.3% of diabetic subjects with values at or above the limit, and 49.9% of those with values below (log rank test p = 0.0082) had died. The corresponding values for non-diabetic subjects were 44.4% and 21.0%, respectively (log rank test p = 0.0002). In single factor log rank tests ischaemic heart disease and a low value of HDL were also predictive of death in the diabetic population during a 10-11-year observation period. In the non-diabetic population ischaemic heart disease, hypertension, and a serum creatinine level above the median value were predictive. In further log rank analyses probands dying during the first years, (e.g. the first 2 years) were removed from the calculations. The prognostic value of the above-mentioned factors diminished with time. In a Cox Regression analysis we found that the predictive value of urinary albumin excretion rate to mortality had disappeared when subjects who had died during the first 5 years were removed from the analysis, whereas HDL in the diabetic patients and blood pressure and serum creatinine in non-diabetic subjects were still of significant predictive value. We therefore conclude that urinary albumin excretion rate is a more short-term predictor of mortality than previously thought, in contrast to HDL, hypertension and serum creatinine.     

Prognostic factors for neutropenic patients in an intensive care unit: respective roles of underlying malignancies and acute organ failures

The response of caprine macrophages to exposure to caprine arthritis-encephalitis virus (CAEV) and lipopolysaccharide (LPS) was investigated in female Nubian and Nubian crossbreed of goats. Macrophages were matured in vitro from monocytes isolated from blood of control and CAEV-infected goats and the concentrations of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in culture supernatant after exposure of cells to LPS and virus were assayed. Though barely detectable in unstimulated cells, TNF-alpha and IL-6 levels showed peak values of 420 +/- 28 to 530 +/- 32 and 70 +/- 27 to 93 +/- 29, respectively, in supernatants of control goat cells [corrected], remaining high through 24 hrs. post treatment with LPS stimulation. Exposure of these control goat cells [corrected] to virus induced lower secretions (p<0.05) of the cytokines. The peak values occurred between 6 and 12 hrs. post treatment with LPS or virus. Cells prepared from virus-infected goats and treated with the mitogen or virus showed significantly (p<0.05) lower response than those from control goats. The present results suggest a dysregulation, possibly downregulation of the production of both cytokines in macrophages of goats chronically diseased by lentivirus infection.     

Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients

BACKGROUND: Long term results after liver resection for hepatocellular carcinoma (HCC) are disappointing because the disease tends to recur. In this study, the authors assessed prognostic factors affecting long term outcome, in the hope that these factors might be used in selecting HCC patients for surgery. METHODS: During the period 1977-1995, 100 consecutive patients underwent curative liver resection; 78 of 100 had HCC arising on preexisting cirrhosis (53 Child's Class A and 25 Child's Class B). Thirty-five prognostic factors were evaluated for their association with overall survival (OS) and disease free survival (DFS) in univariate and multivariate analysis (Cox proportional hazards model). RESULTS: There were four postoperative deaths. Seven patients died in hospital of hepatorenal failure: six had Child's Class B cirrhosis and had undergone preoperative chemoembolization. Of the remaining 89 patients, 50 developed recurrence. All surviving Child's Class B patients had recurrence. Five-year OS, postoperative deaths included, was 38% (median, 36 months). Five-year DFS, postoperative deaths excluded, was 26% (median, 21 months). Independent prognostic factors for DFS were Child's class, glutamic-oxaloacetic transaminase, gamma-glutamyltransferase, alpha-fetoprotein, number of tumor nodules, width of resection margins, preoperative chemoembolization, and experience of the team that performed the surgery. Factors with an independent effect on OS were Child's class and width of resection margins. CONCLUSIONS: Liver resection can provide long term DFS in HCC patients with normal liver function. In patients with liver function impairment or an inadequate resection margin, recurrences are almost certain to occur. Preoperative chemoembolization significantly prolongs DFS but may increase the risk of postoperative liver failure in patients with liver function impairment.     

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel

PURPOSE: Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS: Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS: One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION: As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.     

Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients

We retrospectively investigated the feasibility and the toxicity of autologous stem cell transplantation (ASCT) in 21 cases of systemic amyloidosis (AL). The conditioning regimens consisted of high-dose melphalan (HDM) alone (n = 18) or in combination with 12 Gy total body irradiation (n = 3). Toxic death rate was high: 9/21 patients (43%) died within the first month following ASCT, and 10/12 surviving patients achieved a response. With a median follow-up of 14 months, the OS and the EFS rates at 4 years were 57.1% (+/-10.8) and 29.9% (+/-14.5) respectively for the whole group. The major prognostic factor for both response and survival was the number of clinical manifestations at the time of ASCT, of the following five criteria, i.e. creatinine clearance < 30 ml/min, nephrotic syndrome with urinary protein excretion > 3000 mg/24 h, congestive heart failure, neuropathy, or hepatomegaly associated with alkaline phosphatase level > 200 IU/l. For patients presenting with two or more clinical manifestations the 4-year OS and EFS were both 11.1% compared with 91.7% and 46.3% respectively in patients with fewer than two clinical manifestations at the time of ACST. We conclude that ASCT is feasible in AL in a subset of patients with fewer than two clinical manifestations at the time of ASCT. Given the severe extra-haematological toxicity, ASCT should not be considered in other cases.     

The risk of acute leukemia in patients treated for Hodgkin's disease is significantly higher aft [see bined modality programs than after chemotherapy alone and is correlated with the extent of radiotherapy and type and duration of chemotherapy: a case-control study

BACKGROUND AND OBJECTIVE: Patients treated for Hodgkin's disease have an increased risk of developing subsequent acute leukemia. This co-operative study was conducted to assess the relative risk associated with several candidate factors including age, splenectomy, combined modality therapy and cumulative drug dose including alkylating agents and nitrosurea derivatives. DESIGN AND METHODS: This study evaluated the risk of acute leukemia according to pretreatment variables and therapy modalities among 1659 patients treated for Hodgkin's disease and followed for a median time of 10 years. Both case-control and actuarial risk studies were performed. Median age was 34 years (range: 12-83); 53% of patients were splenectomized. As to the overall therapy, 348 patients (21%) were given radiotherapy (RT) alone, 375 (23%) chemotherapy (CT) alone (including MOPP, MOPP + ABVD or MOPP + ABVD + lomustine); 936 (56%) received both CT and RT, either as primary or salvage treatment. RESULTS: The overall 15-year actuarial risk of leukemia was 4.2%; the hazard function curve showed two peaks of risk at the 3th and the 8th year from the initiation of therapy and no leukemia beyond the 12th year of follow-up. Risk of leukemia was 0.3% after RT alone, 2.8% after CT alone (2.2% after MOPP; 4.4% after MOPP + ABVD + lomustine), and 5.4% in patients given combined modality therapy (10.2% for RT + MOPP; 15.6% for RT + MOPP + lomustine). No leukemia occurred after ABVD alone and the risk was low (0.6%) when neither mechlorethamine nor lomustine were utilized. Patients who had received extended radiotherapy including abdomen and pelvis in addition to MOPP showed a significantly higher risk of leukemia compared to those given limited RT + MOPP (P = 0.01). Case-control analysis indicated advanced stage, type and duration (> 8 months) of CT and extension of RT as significant risk factors for leukemia. Compared to RT alone, the odds ratio was 5.9 after MOPP + extended RT, and 8 when a lomustine-containing regimen was used, as well. Neither age nor splenectomy were independent risk factors for leukemia; splenectomy was influential only when patients had been given MOPP chemotherapy, as well. INTERPRETATIONS AND CONCLUSIONS: Both case-control and actuarial analyses indicated that: a) combined modality therapy with MOPP and extensive RT (including abdomen and pelvis), and the use of lomustine added to the leukemogenic risk of MOPP alone; b) programs without mechlorethamine, procarbazine and lomustine were almost devoid of leukemogenic risk.