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Biomedical subjects

P E Postmus

Publications and source records attributed to P E Postmus.

At least 19 recordsLinked to original sources
PubMed2000

Second-line chemotherapy in relapsing or refractory non-small-cell lung cancer: a review.

PURPOSE: Since the increased use of first-line chemotherapy for non-small-cell lung cancer (NSCLC), second-line chemotherapy may nowadays be considered for a growing group of patients. Guidelines for second-line treatment have to be developed yet. METHODS: We reviewed the published literature on second-line chemotherapy for NSCLC with emphasis on the role of factors such as pretreatment, response to first-line treatment, and length of disease-free-interval. RESULTS: Thirty-four single-agent-studies and 24 multidrug-studies on second-line treatment were identified. Docetaxel has been studied most extensively and is the only agent that has been studied in randomized phase III trials. Different definitions of sensitivity applied by different authors and conflicting results have been reported about the influence of response to prior chemotherapy. CONCLUSION: Since most patients are treated with a platinum-based regimen in the first line, platinum resistance usually is a major consideration for the use of second-line agents. We argue, however, that a more general definition of drug resistance is more appropriate than resistance to platinum only. Criteria to select NSCLC patients for second-line treatment have not been defined yet. This is also important in light of the upcoming necessity to test new drugs in pretreated instead of treated patients. Guidelines for second-line treatment of NSCLC based on clinical information on drug sensitivity to first-line therapy need to be developed.

Antineoplastic Agents↗
PubMed2000

Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

Adult↗
PubMed2000

Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods.

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is considered a valuable tool in the diagnosis and staging of cancer. In addition, it seems promising as a technique to monitor response to therapy. Progress is hampered, however, by the fact that various methods for the analysis of uptake of FDG in tumours have been described and that it is by no means clear whether these methods have the same sensitivity for monitoring response to treatment. As interest in monitoring response using FDG PET is growing, the danger exists that non-optimal methods will be used for evaluation. Hence an overview of the various analytical methods is given, highlighting both advantages and shortcomings of each of the methods. The ideal analytical method for response monitoring should represent an optimal trade-off between accuracy and simplicity (clinical applicability). At present, that trade-off still needs to be defined. Studies relating response, as measured with any of the available analytical methods, to outcome are urgently needed. Until then response monitoring studies should be conducted in such a way that all analytical methods can be compared with the most quantitative one, which at present is full compartmental modelling of the data.

Fluorodeoxyglucose F18↗
PubMed2000

Availability of diagnostic facilities in the Netherlands for patients with suspected pulmonary embolism. ANTELOPE Study Group. Advances in New Technologies Evaluating the Localisation of Pulmonary Embolism.

Pulmonary embolism remains a complex diagnostic problem. Although accurate and cost-effective, the 'Dutch consensus' strategy is not widely applied. We assessed the availability and investment plans of the different facilities used in this strategy. Furthermore, the current and future availability of new diagnostic modalities was investigated. A questionnaire was sent to all Dutch hospitals. The questionnaire contained separate sections with questions for the hospital management and the medical practitioners at the departments of radiology, nuclear medicine, internal medicine and pulmonology. Five hundred and eighty-four questionnaires were sent out (response rate 68%). Forty-three percent of the hospitals had no nuclear medicine facility, 11% had no pulmonary angiography facility, and 59% had no spiral CT scan (SCTA). Forty-six percent of the responding hospitals had a nuclear medicine facility; and 5% used Technegas for ventilation studies. Strategies with SCTA were available in about 27% of the hospitals. Due to future investments this number will increase to approximately 55%. Strategies with Technegas were available in 2.4% of the hospitals, this number might increase to 25% if Technegas is proven accurate. The 'Dutch consensus' strategy is available in two-thirds of the hospitals. All other strategies were less feasible. Several equivalent strategies for diagnosing pulmonary embolism should be developed. These strategies should be accurate, widely available and accepted.

Algorithms↗
PubMed2000

A phase I-II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients.

Thirty patients with chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200 mg/m2) on day 1 in three consecutive cycles, together with a fixed dose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles were repeated every three weeks. The dose escalation of paclitaxel was feasible in the majority of patients. Subsequently, 30 other NSCLC patients received a dose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2 in a phase II study. The major side effect was mild myelosuppression. A response rate of 24% was achieved in 49 fully evaluable patients. This regimen proved to be safe and easy to administer on an out-patient setting, and constitutes now one of the arms of the current EORTC randomized study for advanced NSCLC.

Antimetabolites, Antineoplastic↗
PubMed2000

Untreated idiopathic aneurysm of the pulmonary artery; long-term follow-up.

A 57-year-old man with an idiopathic aneurysm of the left pulmonary artery is presented. The aneurysm was stable over many decades. No such long-term follow-up of an idiopathic pulmonary aneurysm has been described previously. After 39 years there is no evidence of heart failure or pulmonary hypertension. Because corrective surgery has a variable outcome, and prognosis is suggested to be good in the idiopathic form of pulmonary aneurysm, no surgical correction was proposed.

Aneurysm↗
PubMed2000

Regional pressure volume curves by electrical impedance tomography in a model of acute lung injury.

OBJECTIVE: A new noninvasive method, electrical impedance tomography (EIT), was used to make pressure-impedance (PI) curves in a lung lavage model of acute lung injury in pigs. The lower inflection point (LIP) and the upper deflection point (UDP) were determined from these curves and from the traditional pressure-volume (PV) curves to determine whether the PI curves resemble the traditional PV curves. Furthermore, regional differences in the mentioned determinants were investigated. DESIGN: Prospective, experimental study. SETTING: Animal research laboratory. INTERVENTIONS: In nine anesthetized pigs, repeated lung lavage was performed until a Pao2 <80 torr was reached. Thereafter, an inspiratory PV curve was made using a constant flow of oxygen. During the intervention, EIT measurements were performed. MEASUREMENTS AND MAIN RESULTS: In this study, the LIP(EIT) was within 2 cm H2O of the LIP(PV). Furthermore, it was possible to visualize regional PI curves by EIT. No significant difference was found between the LIP(PV) (21.3+/-3.0 cm H2O) and the LIP(EIT) of the total lung (21.5+/-3.0 cm H2O) or the anterior parts of the lung (21.5+/-2.9 cm H2O). A significantly higher LIP (29.5+/-4.9 cm H2O) was found in the posterior parts of the lung. A UDP(PV) could be found in three animals only, whereas in all animals a UDP(EIT) could be determined from the anterior part of the lung. CONCLUSIONS: Using EIT, determination of LIP and UDP from the regional PI curves is possible. The obtained information from the regional PI curves may help in understanding alveolar recruitment. The use of this new bedside technique for clinical decision making remains to be examined.

Animals↗
PubMed2000

Prediction of peak oxygen uptake in men using pulmonary and hemodynamic variables during exercise.

PURPOSE: Many attempts have been made to predict peak VO2 from data obtained at rest or submaximal exercise. Predictive submaximal tests using the heart rate (HR) response have limited accuracy. Some tests incorporate submaximal gas exchange data, but a predictive test without gas exchange measurements would be of benefit. Addition of stroke volume and pulmonary function (PF) measurements might increase the predictability of a submaximal exercise test. METHODS: In this study, an incremental exercise test (10 W x min(-1)) was performed in 30 healthy men of various habitual activity levels. Step-wise multiple regression analysis was used to isolate the most important predictor variables of peak VO2 from a set of measurements of PF: lung volumes, diffusion capacity, airway resistance, and maximum inspiratory and expiratory pressures; gas exchange; minute ventilation (V(E)), tidal volume (V(T)), respiratory exchange ratio (RER = carbon dioxide output divided by VO2); and hemodynamics (HR, stroke index (SI) = stroke volume/body surface area, and mean arterial pressure). These measurements were made at rest and during submaximal exercise. RESULTS: Using the set of PF variables (expressed as percentages of predicted), FEV1 explained 30% of the variance of peak VO2. No other PF variables were predictive. After addition of resting hemodynamic data, SI was included in the prediction equation, raising the predictability to 40%. At the 60-W exercise level, 48% of the variance in peak VO2 could be explained by SI and FEV1. At 150 W, the prediction increased to 81%. At this level VCO2/O2 (RER) also entered the prediction equation of peak VO2: 6.44 x FEV1(%) + 13.0 x SI - 1921 x RER + 2380 (SE = 142 mL x min(-1) x m(-2), P < 0.0001). Leaving out the gas exchange variable RER, maximally 64% of the variance in peak VO2 could be explained. CONCLUSION: In conclusion, inclusion of pulmonary function and hemodynamic measurements could improve the prediction accuracy of a submaximal exercise test. The submaximal exercise test should be performed until a level of 150 W is reached. Noninvasive stroke volume measurements by means of EIC have additional value to measurement of HR alone. Finally, measurement of gas exchange significantly improves the predictability of peak VO2.

Adult↗
PubMed2000

The degree of branching of the glycans of alpha(1)-acid glycoprotein in asthma. A correlation with lung function and inflammatory parameters.

Alpha(1)-acid glycoprotein (AGP) is a plasma protein belonging to the group of acute-phase proteins. It contains five N-linked glycans which, depending on pathophysiologic state, differ in their degree of branching (i.e., in the relative proportions of di-, tri-, and tetraantennary glycans). Changes in the degree of branching of these glycans have been shown to affect various immunomodulatory properties of AGP. We wanted to investigate whether changes occur in the branching of AGP glycans in plasma and in bronchoalveolar lavage fluid (BALF) in asthma. For this purpose, we selected three groups of patients for study: patients with atopic asthma (AA), atopic nonasthmatic patients, and a group of patients with various interstitial lung diseases (ILDs). The plasma AGP concentration was normal in both atopic study groups, but was increased in ILD patients. In contrast, the branching of glycans of AGP was altered in subjects with AA, whereas it was normal in the other study groups. The presence of asthma symptoms correlated with the increased glycan branching of AGP in both plasma and BALF. Additionally, the degree of branching of AGP in BALF was related to FEV(1), to the provocative dose of histamine causing a 20% decrease in FEV (PD(20)), and to the number of eosinophils. In conclusion, asthma is accompanied by changes in the branching of AGP glycans that indicate an inflammatory reaction that differs markedly from a normal acute-phase response, in which decreased branching of AGP occurs.

Adolescent↗
PubMed2000

Do bullae indicate a predisposition to recurrent pneumothorax?

A relationship between idiopathic spontaneous pneumothorax (ISP) and visible parenchymal bullae and blebs has been reported. The causal relationship between blebs and bullae and ISP is questionable. Consequently, resection of the involved area is only indicated if it predisposes to recurrence of the pneumothorax. CT studies on 101 cases of ISP were analysed. The presence of bullae and their distribution was then related to the first and recurrent pneumothorax. CT demonstrated bullae in 56% of first ISP and in 64% of recurrent ISP, mostly among older patients. Only eight patients had bullae larger than 2 cm on the side of the pneumothorax. The location of the bullae was not a factor in predicting recurrent pneumothorax.

Adult↗
PubMed2000

High-resolution CT in patients with intraluminal typical bronchial carcinoid tumors treated with bronchoscopic therapy.

STUDY OBJECTIVE: To evaluate the extent to which high-resolution CT (HRCT) can predict the clinical outcome of bronchoscopic treatment with curative intent in patients with intraluminal typical bronchial carcinoid tumors. DESIGN: An observational study. SETTING: Bronchoscopy unit and radiology department of a university hospital. PATIENTS AND INTERVENTIONS: Eighteen patients with intraluminal typical bronchial carcinoid tumors in the absence of nodal and distant disease were treated with bronchoscopic electrocautery or Nd-YAG laser as an alternative to surgical resection. Prior to treatment, HRCT was performed. RESULTS: In 10 patients, HRCT showed no peribronchial tumor extension, and 9 of these patients were found to be tumor free after bronchoscopic treatment. So far during follow-up, none of these patients has had a recurrence of the tumor. The median duration of follow-up was 33 months (range, 13 to 68 months). In five patients, HRCT showed signs of peribronchial tumor extension. In three of these patients, specimens taken from biopsies performed after bronchoscopic treatment showed residual tumors, and salvage surgery was carried out. In three patients, HRCT was unable to assess peribronchial tumor extension: in two because of insufficient connective tissue contrast between the hilar structures and in one patient because of suboptimal scan technique. CONCLUSION: HRCT findings were complementary but not conclusive in patients with intraluminal typical bronchial carcinoid tumors treated with bronchoscopic therapy. However, in a category of patients in whom HRCT showed strictly intraluminal tumors, bronchoscopic resection as an alternative for surgical resection seems justified.

Adult↗
PubMed2000

Tissue effects of bronchoscopic electrocautery: bronchoscopic appearance and histologic changes of bronchial wall after electrocautery.

STUDY OBJECTIVES: To study tissue effects of bronchoscopic electrocautery (BE). DESIGN: In six patients with non-small cell lung cancer, a BE procedure was performed immediately before surgery. After patients were placed on ventilation, normal mucosa on different carinae was treated with a cautery probe (2-mm(2) surface area) at a power setting of 30 W with a variable time of application of 1 to 5 s. Bronchoscopic appearance of the treated area was documented photographically, and histologic changes of the bronchial wall were examined. SETTING: Bronchoscopy unit of a university hospital. MEASUREMENTS AND RESULTS: BE resulted bronchoscopically in whitening of the bronchial mucosa with crater-shaped lesions. After longer duration of BE application, deeper craters with more profound charring were seen. Histologic changes of the lesions showed craters containing a variable amount of necrotic tissue. In one case, thin subsegmental carinae were coagulated and measurements could not be performed. In the remaining five cases, microscopic findings revealed 0.2 +/- 0.1-mm necrosis after 1 s; 0.4 +/- 0.2-mm necrosis after 2 s; 0.9 +/- 0.5-mm necrosis after 3 s; and 1.9 +/- 0.8-mm necrosis after 5 s. A variable degree of tissue damage surrounding the necrotic tissue area was found. In one case, cartilage damage appeared after 3 s of coagulation, and extensive damage of the underlying cartilage was seen in four cases after 5 s of application. CONCLUSIONS: Superficial damage was obtained by short duration of BE (< or = 2 s), and longer duration of coagulation (3 s or 5 s) caused damage to the underlying cartilage. Bronchoscopic appearance after endobronchial electrocautery corresponded with the histologic changes.

Adult↗
PubMed2000

Outcome of bronchial carcinoma in situ.

INTRODUCTION: The proportion of patients with carcinoma in situ in whom invasive cancer will develop is not known. It is important for clinical decision making to know the outcome of these lesions. The same applies for studies assessing the effectiveness of chemoprevention treatment or endobronchial therapy. METHODS: The records of patients with a bronchial carcinoma in situ who had undergone autofluorescence bronchoscopic examinations at regular intervals during a follow-up period for at least 6 months were reviewed. Data were examined for the outcome of carcinoma in situ, and for the detection, course, and bronchoscopic findings of neoplastic lesions at other bronchial sites. RESULTS: Progression to carcinoma occurred in five of nine patients (56%) with a carcinoma in situ. Eight neoplastic lesions were detected at other sites in four of the nine patients (44%). In earlier biopsy specimens of two sites that later showed a severe dysplasia and a carcinoma, only normal epithelium was found. Biopsies had been performed at these sites because they were assessed as suspicious during autofluorescence bronchoscopy. CONCLUSION: The majority of sites showing a carcinoma in situ progressed to invasive carcinoma. A considerable portion of the patients had neoplastic lesions at other bronchial sites. The fluorescence pattern of the bronchial mucosa may reflect early changes that are not found at histopathologic examination, but which may progress to neoplastic growth.

Aged↗
PubMed1999

[Role of chemo(radio)theray prior to surgery for stage IIIa non-small cell lung carcinoma (localized non-resectable tumor)].

Neoadjuvant chemotherapy with or without combined radiotherapy followed by surgery may yield a survival profit for selected patients with non-small cell lung carcinoma in stage IIIA. It has not yet been established which is the most efficacious neoadjuvant chemotherapy nor what is the best postneoadjuvant chemotherapy, especially resection or radiotherapy. Comparative clinical studies to find the answer to these two questions are in progress. New forms of treatment are required in order to achieve 5-year survival in more stage IIIA patients than is currently the case.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy.

A limitation of photodynamic therapy is the lack of tumor selectivity of the photosensitizer. To overcome this problem, a protocol was developed for coupling of meta-tetrahydroxyphenylchlorin (mTHPC), one of the most promising photosensitizers, to tumor-selective monoclonal antibodies (MAbs). mTHPC was radiolabeled with 131I to facilitate the assessment of the in vitro and in vivo behavior. After the modification to 131I-mTHPC-(CH2COOH)4, thus increasing the water solubility and creating a functional moiety suitable for coupling, conjugation was performed using a labile ester. Insoluble aggregates were not formed when mTHPC-MAb conjugates with a molar ratio of up to 4 were prepared. These conjugates showed a minimal impairment of the integrity on SDS-PAGE, full stability in serum in vitro, and an optimal immunoreactivity. To test the in vivo behavior of the mTHPC-MAb conjugates, the head and neck squamous cell carcinoma-selective chimeric MAb U36 was used in head and neck squamous cell carcinoma-bearing nude mice. Biodistribution data showed that the tumor selectivity of cMAb U36-conjugated mTHPC was increased in comparison with free mTHPC, despite the fact that conjugates with a higher mTHPC:MAb ratio were more rapidly cleared from the blood. Preliminary results on the in vitro efficacy of photodynamic therapy with MAb-conjugated mTHPC showed that mTHPC coupled to the internalizing murine MAb 425 exhibited more phototoxicity than when coupled to the noninternalizing chimeric MAb U36.

Animals↗
PubMed1999

Combination chemotherapy studies with gemcitabine and etoposide in non-small cell lung and ovarian cancer cell lines.

Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and etoposide (4'-demethylepipodo-phyllo-toxin-9-4,6-O-ethylidene-beta-D-g lucopyranoside, VP-16) are antineoplastic agents with clinical activity against various types of solid tumors. Because of the low toxicity profile of dFdC and the differences in mechanisms of cytotoxicity, combinations of both drugs were studied in vitro. For this purpose, we used the human ovarian cancer cell line A2780, its cis-diammine-dichloroplatinum-resistant and VP-16 cross-resistant variant ADDP, and two non-small cell lung cancer cell lines, Lewis Lung (LL, murine) and H322 (human). The interaction between the drugs was determined with the multiple drug effect analysis (fixed molar ratio) and with a variable drug ratio. In the LL cell line, the combination of dFdC and VP-16 at a constant molar ratio (dFdC:VP-16 = 1:4 or 1:0.125 after 4- or 24-hr exposure, respectively) was synergistic (combination index [CI], calculated at 50% growth inhibition = 0.7 and 0.8, respectively; CI <1 indicating synergism). After 24- and 72-hr exposure to both drugs at a constant ratio, additivity was found in the A2780, ADDP, and H322 cell lines (dFdC:VP-16 = 1:500 for both exposure times in these cell lines). When cells were exposed to a combination of dFdC and VP-16 for 24 or 72 hr, with VP-16 at its IC25 and dFdC in a concentration range, additivity was found in both the LL and H322 cells; synergism was observed in the A2780 and ADDP cells, which are the least sensitive to VP-16. Schedule dependency was found in the LL cell line; when cells were exposed to dFdC 4 hr prior to VP-16 (constant molar ratio, total exposure 24 hr), synergism was found (CI = 0.5), whereas additivity was found when cells were exposed to VP-16 prior to dFdC (CI = 1.6). The mechanism of interaction between the drugs was studied in more detail in the LL cell line; dFdCTP accumulation was 1.2-fold enhanced by co-incubation with VP-16, and was even more pronounced (1.4-fold) when cells were exposed to VP-16 prior to dFdC. dCTP levels were decreased by VP-16 alone as well as by the combination of both compounds, which may favor phosphorylation of dFdC, thereby increasing dFdCTP accumulation. DNA strand break (DSB) formation was increased for exposure to both compounds together compared to exposure to each compound separately, this effect being most pronounced when cells were exposed to VP-16 prior to dFdC (38% and 0% DSB for dFdC and VP-16 alone, respectively and 97% DSB for the combination). The potentiation in DSB formation might be a result of the inhibition of DNA repair by dFdC. Provided the right schedule is used, VP-16 is certainly a compound eligible for combination with dFdC.

Antineoplastic Combined Chemotherapy Protocols↗