Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis

The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57-0.86) in seven studies on stages I-II NSCLC; 0.50 (0.39-0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76-1.10) in six studies on any stage NSCLC; 0.57 (0.41-0.78) in five studies on squamous cell cancer; 0.75 (0.61-0.93) and 0.71 (0.61-0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73-1.16) for four studies on small cell lung cancer; 1.26 (0.58-2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.     

The constipation-inducing potential of morphine and transdermal fentanyl

Constipation is an almost universal side-effect associated with chronic opioid analgesia. The resulting discomfort can for some patients be more severe than the pain itself, leading to a reduction of analgesic use and consequently to increased pain. Clinical trials consistently show less constipation in patients treated with transdermal fentanyl than in patients receiving oral morphine. Several reasons can be identified for this finding: owing to its higher lipophilicity, fentanyl penetrates the blood-brain barrier more easily and lower dosing is possible; owing to the transdermal route of administration of fentanyl, comparatively less opioid is available in the gastrointestinal tract to block local opioid receptors; finally, the transdermal route of administration leads to stable plasma levels of fentanyl over 72 h and hence minimises the probability of overdosing that can occur with multiple daily dosing. Further research is needed to establish whether these effects can also be extrapolated to other peripheral effects of opioids such as nausea and vomiting.     

Analytical and clinical evaluation of creatine kinase MB mass assay by IMx: comparison with MB isoenzyme activity and serum myoglobin for early diagnosis of myocardial infarction.

We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin.     

Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism

Objective To describe the use of volumetric capnography, a plot of expired CO₂ concentration against expired volume, in monitoring fibrinolytic treatment of major pulmonary embolism.Design and setting Two case reports in the emergency department of a teaching hospital.Patients Two conscious and spontaneously breathing patients (69- and 31-year-old women) with major pulmonary embolism requiring thrombolysis. Decision for thrombolysis was based on the association of right ventricular afterload on echocardiography, with respiratory failure and hypotension in the first patient, and dyspnea and hemodynamically stable parameters in the second one.Interventions Successive capnographic measurements were performed before, during, and after thrombolysis. Curves of volumetric capnography were obtained from a sidestream gas monitor with flow sensor and an arterial blood gas analysis for CO₂ partial pressure.Measurements and results We calculated late deadspace fraction, previously suggested as the most effective capnographic parameter in the diagnosis of pulmonary embolism. Late deadspace fraction decreased in the two patients, respectively, from 64.4% to 1.1% and from 25.6% to 5.7% after thrombolysis, with a concomitant disappearance of right heart dysfunction signs on echocardiography.Conclusions Volumetric capnography can monitor thrombolysis in major pulmonary embolism. Differences between volumetric capnography technology and the more traditional arterial to end-tidal CO₂ gradient are important to take into account for clinical application.     

Prospective Evaluation of the Change of Predialysis Protein‐Bound Uremic Solute Concentration With Postdilution Online Hemodiafiltration

Although protein‐bound uremic compounds have been related to outcome in observational studies, few current dialysis strategies provide more removal of those compounds than standard hemodialysis. We evaluated the evolution of protein‐bound uremic solutes after a switch from high‐flux hemodialysis to postdilution hemodiafiltration (n = 13). We compared predialysis solute concentration at 4, 5, and 9 weeks versus baseline for several protein‐bound compounds and water‐soluble solutes, as well as for β₂‐microglobulin. After 9 weeks of postdilution hemodiafiltration, a significant decrease versus baseline could be detected for total concentration of protein‐bound solutes: p‐cresylsulfate (3.98 ± 1.51–3.17 ± 1.77 mg/dL, ?20%, P < 0.01) and 3‐carboxyl‐4‐methyl‐5‐propyl‐2‐furanpropionic acid (0.72 ± 0.52–0.64 ± 0.46 mg/dL, ?11%, P < 0.01). For the other protein‐bound solutes, hippuric acid, indoleacetic acid, and indoxylsulfate, no change in total concentration could be detected. The concentration of the middle molecule, β₂‐microglobulin, decreased as well after 9 weeks of postdilution hemodiafiltration (24.7 ± 9.3–18.1 ± 6.7 mg/L, ?27%, P < 0.01). For water‐soluble compounds, no significant change of concentration was found. Postdilution hemodiafiltration in comparison to high‐flux hemodialysis provided significant reduction of predialysis concentration of protein‐bound compounds, especially those with the highest protein binding, and of β₂‐microglobulin, by ?11 to ?27% in 9 weeks.     

Non-heart-beating donor, 10-year experience in a Belgian transplant center

All over the world, transplant teams are looking for ways to increase and improve the donor pool. Non-heart-beating donation may increase the number of donors, even if some technical, logistical, and emotional problems are still encountered. The results obtained by our team should stimulate other centers to implement this kind of donation in their hospitals. Herein we have described our experience with non-heart-beating donation.     

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy.     

The role of intensive care in managing childhood cancer

To study the value of intensive care in childhood cancer, we evaluated the clinical course and outcome of all such children admitted to our intensive care unit (ICU) (n = 183) during the five-year period from 1984-1988. Excluding those admitted for postoperative observation, there were a total of 63 admissions for complications of malignancy. Of these, admissions for sepsis, pulmonary parenchymal disease, or coma were associated with poor outcome. Thirty-six percent of patients requiring mechanical ventilation for respiratory failure and 27% requiring inotropic support survived longer than six months. Physiologic Stability Index and Therapeutic Intervention Scores were significantly greater in nonsurvivors than survivors. Of those who survived their ICU stay, 50% went home functioning at their premorbid state. The duration of ICU stay was not different in survivors and nonsurvivors, suggesting that intensive care does not excessively prolong the dying process. We conclude that many life-threatening complications of cancer are potentially reversible. The extent of functional recovery of survivors warrants aggressive intensive support in this setting.     

P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production.

BACKGROUND: Chronic renal insufficiency is associated with the retention of solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound uraemic retention solute, has been shown to exert toxic effects in vitro. Recently, however, it has been demonstrated that p-cresol in the human body is conjugated, with p-cresylsulphate as the main metabolite. METHODS: The present study evaluates the effect of p-cresylsulphate on the respiratory burst activity of leucocytes. RESULTS: P-cresylsulphate significantly increased the percentage of leucocytes displaying oxidative burst activity at baseline. Oxidative burst activity of stimulated leucocytes was however not affected. In contrast, p-cresol had no effect on the leucocytes at baseline, but inhibited leucocytes burst activity after stimulation. CONCLUSION: The present study demonstrates, for the first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a pro-inflammatory effect on unstimulated leucocytes. This effect could contribute to the propensity to vascular disease in the uraemic population.