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Biomedical subjects

P E Postmus

Publications and source records attributed to P E Postmus.

At least 37 records · Page 2Linked to original sources
PubMed2003

Epoprostenol therapy for primary pulmonary hypertension after rejection of a single donor lung.

Before prostacyclins became available, lung or heart/lung transplantation was the only effective treatment for patients with primary pulmonary hypertension (PPH) who deteriorated under supportive medical treatment. Unfortunately, acute and chronic rejections occur in a large number of cases, limiting the average survival to 4.5 yrs. A female patient, age 35 yrs, was diagnosed with PPH and underwent single lung transplantation. Despite aggressive immunosuppressive therapy, the patient had several episodes of acute rejection. Eventually, chronic rejection with bronchiolitis obliterans developed. After 5 yrs, the donor lung was no longer functional. The patient was in New York Heart Association (NYHA) class 4, had a 6-min walking distance of 50 m and a resting arterial oxygen tension (Pa,O2) of 9.8 kPa (74 mmHg) when using 3 L x min(-1) of oxygen. Epoprostenol treatment was started and the patient showed remarkable improvement. After 17 months the patient was NYHA class 2, walked 503 m in 6 min and had a resting Pa,O2 of 10.9 kPa (82 mmHg) without supplemental oxygen. In this patient, treatment with epoprostenol was effective after rejection of a single donor lung transplanted for primary pulmonary hypertension.

Adult↗
PubMed2002

Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography.

Electrical impedance tomography (EIT) has been proposed as a method to monitor dynamic changes in the pulmonary vascular bed. In this study we examined the validity of EIT in the measurement of pulmonary vasodilatation in eight patients with primary and secondary pulmonary hypertension when given the vasodilating agent epoprostenol (Flolan). Therefore, catheterization of the pulmonary artery was performed in the ICU and the cardiac output was measured by means of the Fick method. The pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) were determined. Epoprostenol was given in increasing doses to test reversibility of pulmonary hypertension. The maximum test dose was 12 ng kg(-1) min(-1). During each step simultaneous EIT (DAS-01 P Portable Data Acquisition System, Sheffield, England) measurements were performed with the 16 electrodes equidistantly positioned in the third intercostal space. The maximal systolic impedance change, relative to end-diastole, deltaZperf, was chosen as a measure of pulmonary perfusion. The impedance change between baseline and highest tolerable epoprostenol concentration was compared with the change in PVR. The mean PVR (dyn s/cm5) decreased from 636 (+/-399) to 366 (+/-242); p < 0.01. DeltaZperf (in arbitrary units) for the whole patient group increased from 901 (+/-295) x 10(-3) to 1082 (+/-472) x 10(-3) (p<0.05). Only one patient showed a reduction in pulmonary artery pressure >20%, which is defined as significant vasodilatation. A strong relationship was found between the impedance changes and the change in PVR and mPAP in the patient with a significant vasodilatation on epoprostenol. From these results we conclude that EIT is a reliable method to measure blood volume changes due to pharmacologically induced vasodilatation in the pulmonary bed.

Adult↗
PubMed2002

An analysis of chemotherapy dose and dose-intensity in small-cell lung cancer: lessons to be drawn.

BACKGROUND: The survival in untreated small-cell lung cancer (SCLC) is <3 months. Prognosis has improved with chemotherapy, but remains poor. One of the issues concerning current chemotherapy is whether there is any benefit of increasing chemotherapy dose or dose intensity (DI). DESIGN: In the present review, 20 randomised studies, published in the period 1980-2001, in which dose or DI of chemotherapy in SCLC were the only variables tested, are analysed. The studies were categorised as follows: (i) number of cycles (treatment duration); (ii) dose per cycle; (iii) interval between cycles (dose densification); and (iv) a combination of these variables. RESULTS: (i) With treatment duration reduced to three to six cycles, median survival time (MST) was 2 months shorter, most evident in patients showing a (complete) response to initial chemotherapy. (ii) An improved survival was observed in two out of five high-dose studies. (iii) Survival was increased by 0.6 to 6.2 months in all four densification studies. (iv) Survival was not improved in studies that used dose-escalation and/or -densification in combination with a reduced number of cycles. The sample sizes were too small to be conclusive in most of the individual trials. The median of the MSTs in the 20 trials taken together was 9.8 months for the standard arms and 11.5 months for the intensified arms (i.e. more cycles, higher dose per cycle and/or shorter intervals). After omitting the two trials with reduced number of cycles in the so-called 'high-dose' arm, the median of MSTs was 8.7 and 11.5 months, respectively. There was only a slight improvement (1%) in 2-year survival for all trials taken together. However, when only taking high-dose and dose-densified chemotherapy trials into account, the difference in median 2-year survival became 19% (12% versus 31%). CONCLUSIONS: The above classification facilitates our understanding about doses of chemotherapy and it makes us appreciate the relevance of the individual determinants. It appears that the number of cycles, dose level, dose density, cumulative dose and DI are all important factors for improving survival. Intensification of chemotherapy still deserves further research in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Practice, efficacy and cost of staging suspected non-small cell lung cancer: a retrospective study in two Dutch hospitals.

BACKGROUND: A study was undertaken to investigate the clinical practice, yield, and costs of preoperative staging in patients with suspected NSCLC and to obtain baseline data for prospective studies on the cost effectiveness of (18)F-fluorodeoxyglucose positron emission tomography in the management of these patients. METHODS: A retrospective study of the medical records of all patients with suspected NSCLC was performed during a 2 year interval (1993-4) in an academic and a large community hospital. RESULTS: Three hundred and ninety five patients with suspected NSCLC were identified; 58 were deemed to be medically inoperable and 337 patients proceeded to the staging process. Staging required a mean (SD) of 5.1 (1.5) diagnostic tests per patient (excluding thoracotomy) carried out over a median period of 20 days (IQR 10-31). Many of the tests (including both invasive and non-invasive) were done because previous imaging tests had suggested metastases, and in most cases the results of initial tests proved to be false positives. After clinical staging, 168 patients were considered to be resectable (stage I/II) and 144 patients underwent surgery with curative intent. At surgery 33 patients (23% of those who underwent surgery) were found to have irresectable lesions and 19 (13%) had a benign lesion. Surgery was also considered to be futile in 22 patients (15%) who developed metastases or local recurrence within 12 months following radical surgery. Hospital admission was responsible for most of the costs. CONCLUSION: In many patients staging involved considerable effort in terms of the number of diagnostic tests, the duration of the staging period and the cost, with limited success in preventing futile surgery. Failures relate to the quality of diagnostic preparation at every level of the TNM staging system.

Adult↗
PubMed2002

Failure patterns of combined modality treatment in lung cancer: the impact of staging.

BACKGROUND: Patients with locally advanced non-small cell lung cancer (NSCLC) may be treated with induction chemotherapy (IC) followed by surgery with curative intent. The impact of staging inaccuracies on the failure rate of this intensive combined modality treatment approach, i.e. non-curative chemotherapy and thoracotomy, requires further investigation. METHODS: The records of a cohort of 38 consecutive NSCLC IIIA-N2 patients treated with IC followed by surgery were reviewed. RESULTS: The clinical course strongly suggested that the standard diagnostic algorithm failed to demonstrate stage IV disease in 34% of the cases. Surgery instigated by CT-based response criteria at restaging after chemotherapy proved to be irradical in 70% of cases. CONCLUSION: Our data confirm the limitations of the current work-up of patients with apparently locally advanced NSCLC. This applies to the selection of patients to be assigned to combined modality treatment as well as to the post-chemotherapy assessment of resectability. Improved (re)staging of these patients will enhance the efficiency of intervention trials and prevent patients from being exposed to intensive and toxic therapy from which they derive no benefit.

Adult↗
PubMed2001

Accelerated cisplatin and high-dose epirubicin with G-CSF support in patients with relapsed non-small-cell lung cancer: feasibility and efficacy.

The purpose of this study is to determine whether it is feasible to administer high-dose epirubicin (135 mg m(-2)) combined with a fixed dose of cisplatin every 2 weeks with G-CSF support in patients with metastatic non-small-cell lung cancer (NSCLC). Subsequently, the efficacy of the recommended dose of this regimen was tested in a phase II study in patients with relapsed NSCLC. In the initial feasibility study at least 6 patients were entered at each of the 4 dose levels tested. A fixed dose of cisplatin 60 mg m(-2) was given. Epirubicin was administered at 120 mg m(-2) on dose level 1, 135 mg m(-2) on dose level 2 and 3 and 135 mg m(-2) on dose level 4. Patients treated at dose level 3 and 4 received G-CSF support on days 3-12. Cycles were repeated every 3 weeks on the first 3 dose levels and every 2 weeks on the fourth dose level. A total of 27 patients were then treated on dose level 4, which appeared to be feasible in the initial study. In the initial study, a total of 86 courses were administered. Haematological toxicity was the principal side effect. None of the patients encountered dose-limiting toxicity in the first course, which confirmed that epirubicin 135 mg m(-2) could be combined with cisplatin 60 mg m(-2) and accelerated by G-CSF support to a 14-day-schedule. In the subsequent phase II study with this schedule, 89 courses were administered. The relative dose intensity of cisplatin and epirubicin was 0.90 and 0.91, respectively. Myelosuppression was frequent with 70% and 63% of patients experiencing WHO grade III or IV leukocytopenia and thrombocytopenia, respectively. 6 cases of febrile neutropenia were observed, with 2 treatment-related deaths. Non-haematological toxicity consisted mainly of nausea and vomiting, which was grade III in 22% of patients. Renal toxicity grade I and II occurred in 37% and 4% of patients, respectively. 55% of these patients had received prior cisplatin-containing chemotherapy. On an intention-to-treat basis 9 partial responses were recorded in 27 patients (33%; 95% confidence interval, 15%-51%). Accelerated cisplatin and high-dose epirubicin with G-CSF support is a feasible and promising regimen in relapsed NSCLC. Myelosuppression limits the use of this regimen in the second-line setting to a selected group of patients with a good performance status. Since the activity of this regimen is encouraging, it is probably best studied in untreated patients.

Adult↗
PubMed2001

Photodynamic therapy, Nd-YAG laser and electrocautery for treating early-stage intraluminal cancer: which to choose?

The degree of healing and damage of the bronchial wall after photodynamic therapy, Nd-YAG laser and electrocautery for intraluminal early-stage cancer have been analysed. Review of the bronchoscopy reports and follow-up histology specimens of twenty-nine patients treated bronchoscopically with curative intent for their intraluminal tumor have been performed. Seventeen patients had been treated with bronchoscopic electrocautery (BE) only, six with photodynamic therapy (PDT) and six with Nd-YAG laser. Bronchial wall scarring seen during follow-up bronchoscopy was scored and subepithelial fibrosis were histologically evaluated using Alcian blue staining, Azan staining and polarised light. After BE, prominent airway scarring was seen in five patients (29%), with significant stenosis (>50% lumen) in one of these cases. Prominent scarring and significant stenosis were found in four (67%), after PDT. In five (83%) after Nd-YAG laser prominent scarring was found, one patient had significant stenosis. In three cases, two after BE and one after PDT, subepithelial tissue in the follow-up biopsies was insufficient for proper histologic examination. In the remaining biopsy specimen only one (7%) showed a moderate or excessive amount of fibroblasts after BE, whereas for PDT and Nd-YAG this was found in three (60%) and four patients (67%), respectively. Excessive matrix was found in none of the biopsies after BE, in two (40%) after PDT and in three (50%) after Nd-YAG laser. Compact collagen formations were seen in two (12%) biopsies after BE, in two (40 and 33%) after PDT and Nd-YAG, respectively. Compared to electrocautery, more airway scarring and more subepithelial fibrosis were seen after treatment with PDT and Nd-YAG laser. These findings, especially regarding PDT, is in contrast to the assumption that PDT is selective and may be important in the choice of treatment for patients with early stage cancer.

Adolescent↗
PubMed2001

Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.

Resistance to chemotherapy is common in non-small cell lung cancer. The aim of this study was to investigate the prognostic impact of in vitro established drug resistance markers on the response to chemotherapy in patients with advanced non-small cell lung cancer. Samples of 38 patients were analyzed by immunohistochemical staining, for topoisomerase IIalpha and IIbeta, Ki-67, MRP and LRP. In addition, mutation analysis of the topoisomerase IIalpha gene, the B/DNBS and the Tyr804 region, was performed. Lung tumor biopsies were taken prior for treatment with one of the following regimens; cisplatin/paclitaxel, cisplatin/VM26 or VP16, or carboplatin/VP16/ifosfamide. Seventeen patients obtained a partial response, 12 had stable disease and nine patients had progressive disease. None of the investigated markers was related with overall response rate. In one sample a point mutation in the B/DNBS region of the topo IIalpha gene was detected which substitutes IIe(510) with Val. This tumor had a partial response to four courses of cisplatin/VP16 treatment. The survival analysis showed that the patients with high topo IIalpha expressing tumors had a significantly worse survival compared with the patients with low or intermediate topo IIalpha expressing tumors. In conclusion, no relation was observed between expression of topoisomerase IIalpha, IIbeta, Ki-67, MRP or LRP and response rate. Furthermore, worse survival was seen in patients with high topoisomerase IIalpha expressing tumors. In one tumor sample, a newly described mutation in the B/DNBS region of the topo IIalpha gene was detected, which does not appear to be related to drug resistance.

ATP-Binding Cassette Transporters↗
PubMed2001

Fluorescence bronchoscopy for early detection of lung cancer: a clinical perspective.

The conventional method of bronchoscopy has only a 30% sensitivity to detect early stage cancer in the central airways. For patients with positive sputum cytology who clearly harbor early cancers, repeat and lengthy sessions of bronchoscopies are required for accurate localization of these lesions. This leads to a significant delay in obtaining the diagnosis, postponing an appropriate treatment and reduces the chance for cure. There are valid reasons for improving the detection rate of early stage lung cancers. The number of individuals at risk forms a large population, the outcome of patients treated with early stage cancer has been shown to be better and bronchoscopic treatments, e.g. photodynamic therapy and electrocautery, are currently alternatives for surgical resection. Finding more early stage cancers by screening the population at risk and accurate staging to enable treatment at the earliest stage feasible, may improve the dismal prognosis of many patients. This article deals with the clinical background and current problems in early detection of lung cancer and discusses our expectations regarding new developments in bronchoscopy for early detection, accurate staging and treatment of lung cancer.

Bronchoscopy↗
PubMed2001

The role of photodynamic therapy in the management of stage I/II NSCLC.

There is a resurgence of interest in lung cancer screening, motivated by the fact that many lung cancer patients cannot be cured due to advanced disease at presentation. Lung cancer screening may detect more early stage disease. Very early stage squamous cell type lung cancer in the central tracheobronchial tree can be detected and local bronchoscopic treatments such as photodynamic therapy can be applied if the tumor is strictly intraluminal and nodal disease is absent. So, accurate staging regarding tumor size and nodal disease is much more important than treatment per se. Bronchoscopic treatments are less morbid treatment alternatives than surgery and surgical bronchoplasty, especially for patients suffering from COPD and who have poor cardiovascular status due to their smoking history.

Bronchoscopy↗
PubMed2001

The application of a Dutch consensus diagnostic strategy for pulmonary embolism in clinical practice.

In The Netherlands, the 'Dutch consensus strategy' was formulated in 1993 as a diagnostic strategy for patients with suspected pulmonary embolism. Four years after its introduction, the application of this strategy was investigated. A questionnaire was sent to the hospital management and the departments of internal medicine and pulmonology of all Dutch hospitals. In total, 384 questionnaires were sent out. The response rates of the internists and pulmonologists were 63 and 65%, respectively. The specialists reported to have followed the consensus strategy in 75% of the patients seen the month prior to the questionnaire. However, analysis of only the last patient with the suspicion of pulmonary embolism revealed that the consensus strategy was followed in 55 of the 162 patients. As well, an overuse and an underuse of the different diagnostic facilities was documented. Furthermore almost a quarter of the patients were treated without an ascertained diagnosis, whereas 11% were not treated despite an improper exclusion of venous thrombo-embolism. Compared to a survey in 1994, the use of the 'Dutch consensus strategy' has not improved dramatically. In 34% of the patients, the consensus strategy was strictly followed (i.e. without any additional investigation); however in 67% of the patients a proper diagnosis was achieved. In any diagnostic strategy, two aspects should be considered. First the availability of the different facilities. Second the acceptance of the strategy by the physicians, involved in the diagnosis of patients with clinically suspected pulmonary embolism.

Algorithms↗
PubMed2001

Exercise-induced spontaneous hemothorax insinuates trauma; yet unmasks a lament disorder.

The investigation for a plausible explanation of the development of massive spontaneous hemothorax during exercise in two patients led to the disclosure of two different malignancies. The first patient (pleural fibrosarcoma) passed away shortly after diagnosis. The second patient is alive without signs of disease (peripheral neuro-ectodermal tumor, PNET) since the diagnosis was made 3 years before. Spontaneous hemothorax (SH) arising during exercise does not exclusively designate trauma and full search for anatomical abnormality is warranted.

Adult↗
PubMed2001

Single-agent gemcitabine in patients with resistant small-cell lung cancer.

OBJECTIVE: This study was conducted to assess the activity and toxicity ofgemcitabine in patients with resistant small-cell lung cancer (SCLC). PATIENTS TAND METHODS: Forty-one patients with limited- or extensive-stage SCLC, who were previously treated with at least one chemotherapeutic regimen and progressed during or within three months of finishing the last regimen, were treated with 1000 mg/m2 gemcitabine on days 1, 8, and 15 of a four-week cycle. RESULTS: Thirty-eight patients were evaluable for response. Five partial and no complete responses were seen, for an overall response rate of 13% (95% confidence interval (CI): 6%-27%). Time to progression varied from 4 to 20 weeks, with a median of 8 weeks. Median survival was 17 weeks (range 4-84 weeks). Hematological toxicity mainly consisted of NCI-CTC grade 3 thrombocytopenia (29% of patients) and, to a lesser extent, grade 3 leukopenia (18% of patients). Non-hematological toxicity was mild, with nausea being the most commonly reported event. CONCLUSIONS: Gemcitabine has modest activity in patients with resistant SCLC. There is some non-cross resistance to most agents against SCLC.

Adult↗
PubMed2001

Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients.

BACKGROUND: Expression of inhibitor of apoptosis family proteins (IAPs) has been shown in vitro to decrease chemosensitivity through caspase inhibition. However, the role of IAPs as predictors of response to chemotherapy in cancer patients remains to be determined. PATIENTS AND METHODS: Using immunohistochemistry, we assessed the expression of the IAP proteins c-IAP1, c-IAP2, and XIAP on tumors from 55 patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy, and correlated that with the observed response to chemotherapy, time to progression and overall survival. RESULTS: Differences were observed in the pattern of staining among the IAP proteins. The expression of c-IAP2 and XIAP was exclusively cytoplasmic. whereas c-IAP1 also displayed nuclear staining. The median expression of tumor cells for c-IAP1, c-IAP2, and XIAP was 70%, 45%, and 25%, respectively, and a correlation was observed between c-IAP1 and c-IAP2 (P = 0.004), and c-IAP1 and XIAP expression (P = 0.013). However, no association was seen between the expression of these proteins and sex, age, tumor size, stage, histology and grade of differentiation. Interestingly, expression of c-IAP1, c-IAP2, and XIAP did not predict response to chemotherapy. In addition, the expression of IAPs had no impact on the time to progression or overall survival of this group of patients. CONCLUSIONS: Our results indicate that: 1) there are differences in the level of expression and in the subcellular distribution of c-IAP1, c-IAP2, and XIAP in tumors derived from NSCLC patients. 2) The expression of c-IAP1, c-IAP2 and XIAP does not predict the response to chemotherapy in patients with advanced NSCLC. 3) The relation between expression of IAPs and chemosensitivity in cancer patients may be more complex than anticipated by in vitro data.

Adult↗