Gunnar Hillerdal

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (75)170.44 Total impact

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    ABSTRACT: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.
    PLoS ONE 01/2013; 8(8):e72030. · 3.73 Impact Factor
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    ABSTRACT: Sequential administration of chemotherapeutic drugs might have advantages: additive toxicity is avoided and the individual drugs can be given in full dosages. The Swedish group earlier found the combination of gemcitabine and carboplatin to be effective and with acceptable toxicity. The group therefore decided to add docetaxel in a sequential way in a randomized phase II study. Patients were randomized to either gemcitabine or carboplatin for six cycles or the same regimen for three cycles followed by weekly single agent docetaxel. The primary objective was time to progression (TTP). One hundred and twenty-three patients with performance status WHO 0-2 and with earlier un-treated non-small cell lung cancer with measurable stage IIIB disease, not amenable to curative treatment, or stage IV disease without known metastatic spread to the CNS, were enrolled. Hematological toxicity was more common in the GC group but clinically significant bleeding or leucopenic fever occurred only in a minority of patients. No complete responses were noted. Partial response (PR) was observed in 19.3% and 20.8% in the GC and GCD group, respectively. Progression-free survival was 5.6 and 4.8 months and overall survival time 10.6 and 10.1 months in the GC and GCD groups, respectively. Thus, sequential treatment with docetaxel after treatment with gemcitabine and carboplatin did not improve time to progression, response rates, or overall survival.
    Lung cancer (Amsterdam, Netherlands) 02/2011; 71(2):178-81. · 3.14 Impact Factor
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    ABSTRACT: The village of Karain, Turkey, has the world's highest prevalence rate of malignant mesothelioma (MM). Environmental exposure to erionite is thought to cause the disease. However, it has also been suggested that the disease is mainly genetic. Residents in Karain village were traced from 1990 to 2006. Mineral samples were obtained from stones used in construction of their houses and any fibers present were identified. All women who had moved to the village as brides were traced and their cause of death determined. MM was the cause of death in 52 of 322 villagers, representing 50.5% of all deaths. Only 2 of 8 types of stones used in construction contained erionite, and these stones had been used almost exclusively in the mid-sections of the village, where MM was common. In houses not containing erionite, no cases of MM were observed. Sixty-four women came as brides to Karain from villages where erionite or asbestos is not found. Of the 16 women who have died, 11 (69%) died from MM. The extreme risk of MM in Karain is due to indoor exposure to erionite. The effect of genetic factors on mesothelioma development cannot be evaluated in this study, but is likely to be minor.
    Archives of Environmental and Occupational Health 01/2010; 65(2):86-93. · 1.19 Impact Factor
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    Y Izzetin Baris, Gunnar Hillerdal
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    ABSTRACT: At least four of the sultans who ruled during the 19th century suffered from tuberculosis (TB), and probably many of the women and children in the harem too. Life there was crowded with low standards of hygiene, resulting in high mortality, especially among children. Infectious diseases were the main killers and TB was one of the many factors behind the decline and fall of the empire.
    Journal of Medical Biography 09/2009; 17(3):170-3.
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    ABSTRACT: Material from 117 consecutive patients with lung cancer was investigated with respect to serological markers for chronic Chlamydia pneumoniae infection. Specific C. pneumoniae IgA antibodies were found significantly more often in patients with lung cancer than in control groups with coronary heart disease and in healthy controls, even after adjustment for smoking. The results suggest that chronic C. pnmmoniae infection is common in patients with lung cancer.
    Apmis 08/2009; 107(7‐12):828 - 832. · 2.07 Impact Factor
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    ABSTRACT: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months. The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2008; 3(11):1325-31. · 4.55 Impact Factor
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    ABSTRACT: Malignant pleural mesothelioma (MPM) has a poor prognosis and there is limited effect of treatment. Lately, pemetrexed and cisplatin have been established as the standard treatment. The present study was planned in 1998, when there was no standard treatment. Single-dose doxorubicine had, in small studies, accomplished remissions, and the Scandinavian Mesothelioma Groups therefore decided to test a liposomized form of this drug, which had shown limited toxicity but good efficacy in a few small studies. Fifty-four evaluable patients with histologically verified and inoperable MPM were treated with liposomized doxorubicine 40 mg/m(2), every 4 weeks for six cycles. In all, 29 patients (54%) received at least six treatments. The quality of life remained good during the study. Hematologic toxicity was very low. Palmo-plantar erythema occurred in 11 patients (20%), thereof 7 grade II but none was severe and none was dose-limiting. There were four partial responses (7%). The median time to progression (TTP) was 5 months, the median survival was 12 months, and at 24 months, 22% were still alive. Liposomized doxorubicine has a low toxicity and is well tolerated; there were a remarkably long TTP and a good survival. Thus, despite the low response rate, liposomized doxorubicine remains an interesting drug for the treatment of malignant mesothelioma.
    The Clinical Respiratory Journal 04/2008; 2(2):80-5. · 1.66 Impact Factor
  • Gunnar Hillerdal
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    ABSTRACT: The present paradigm is that slow-growing and clinically unimportant lung cancers are very rare. Over the years, convincing evidence for their existence in significant numbers has been dismissed, but with computerized tomography scanning being increasingly common, their reality can no longer be denied. The time is now ripe for a paradigm shift--with consequences for screening as well as clinical practice in the future. The doubling time of the tumor is probably the most important factor for survival of the patient, and research on how to measure this figure is urgent. Age, smoking habits, and comorbidities of the patient are now the main factors when discussing treatment with the patient; once we can predict the behavior of the cancer, i.e., whether it is indolent or actually threatens the patient's life, we will be able to give better advice.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2008; 3(3):208-11. · 4.55 Impact Factor
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    ABSTRACT: To evaluate weekly induction chemotherapy followed by weekly concomitant chemoradiotherapy in a multicentre phase II study of patients with unresectable stage III non-small cell lung cancer (NSCLC; stage wet IIIB excluded). Eligible patients received three weekly cycles of paclitaxel 100 mg/m2 and carboplatin AUC2 followed by six weekly cycles of paclitaxel 60 mg/m2 and carboplatin AUC2 in combination with thoracic radiotherapy (2 Gy per fraction and day to a total dose of 60 Gy). Sixty-four patients (40 males and 24 females) with a median age of 63 years (range, 43-79 years) entered the study. T and N stage were distributed as follows: T1 2 patients (3.2%), T2 10 patients (15.6%), T3 15 patients (23.4%), T4 37 patients (57.8%); N0 10 patients (15.6%), N1 1 patient (1.6%), N2 26 patients (40.6%), N3 26 patients (40.6%), and N missing 1 patient (1.6%). Seven patients (10.9%) suffered from grade 3/4 oesophagitis. Grade 1/2 oesophagitis occurred in 36 patients (56.3%) and pneumonitis grade 1/2 occurred in 10 patients (15.6%). Sixty-three patients were evaluated on an intent-to-treat basis. The overall response rate was 74.6%. The median time to progression was 247 days and median overall survival was 461 days. According to subgroup analyses, no statistically significant differences were noted according to gender, age (<65 vs. > or =65 years), performance status, histology, or study centre. Induction chemotherapy followed by concurrent chemoradiotherapy with weekly cycles of paclitaxel and carboplatin is feasible and generates moderate toxicity. Efficacy is comparable to other recently published regimens. However, prognosis remains, in general, poor for this group of patients and further work to develop better therapy is required.
    Anticancer research 01/2008; 28(5B):2851-7. · 1.71 Impact Factor
  • Gunnar Hillerdal
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    ABSTRACT: The yellow nail syndrome (YNS) is the triad of 'yellow' nails, peripheral oedema and pleural effusions. For diagnosis, which is clinical, at least two of these findings are necessary. Also typical is a long-standing chronic cough often caused by low-grade bronchiectases. The pleural effusions often require pleurodesis. The pathogenesis is probably a dysfunction of the lymphatic system (1, 2). Octreotide regulates the release of growth hormone and thyrotropin, and also has effects on the gastro-intestinal tract, where it inhibits glandular secretion, neurotransmission, smooth-muscle contraction and absorption of nutrients. Adverse effects are nausea, abdominal cramps, diarrhoea, malabsorption of fat and flatulence (3). Because of the inhibition of absorption of fats and other nutrients, octreotide has been useful in chylothorax from many different causes (4). The pleural effusion in YNS is usually an exudate, but in rare cases a frank chylothorax. One such case with successful octreotide treatment has been described in the literature (5). The aim of this report was to investigate the effect of octreotide treatment on a patient with YNS with pleural exudates not resulting from chylothorax. A 62-year-old man with typical YNS presented with bilateral large pleural effusions (Fig. 1). He had suffered from repeated pneumonia for many years, and 10 years earlier mild bronchiectases were diagnosed and yellow nails were noted. From the right pleura, 1750-mL clear yellowish fluid was removed and a few days later, 1300 mL was removed from the left side. During the next few weeks, repeated thoracocenteses on both sides were necessary for the palliation of his dyspnoea, and the total amount of removed fluid was more than 10 L. The pleural fluid showed a low cholesterol value, 1.2 mmol/L (serum, 3.5), a fairly high albumin level, 19.0 g/L [serum, 25 g/L (normal, 36-45)], and no triglycerides. Octreotide was administered, initially 0.5 mg subcutaneously twice daily to make sure that there were no side effects, then the long-acting drug, 30 mg given every fourth week. There was a subjective improvement after the first week, and even though he still has pleural effusions bilaterally, he no longer needs palliative thoracocenteses and can live a normal life. His nails are better, as is the oedema. He is satisfied with his treatment and does not wish to have any pleurodesis. The observation time is now 6 months, and no adverse side effects have been seen so far. Octreotide can be tried in cases of YNS before more aggressive therapies are started. However, the best results are probably achieved in the rare cases where the effusion is a chylothorax. The other symptoms, such as yellow nails and oedema, also seemed to improve but evaluation is difficult because even normally, there are variations over time with these symptoms. Pleurodesis will probably be necessary in the future for our patient despite his octreotide treatment. Further studies are warranted in this rare disease.
    The Clinical Respiratory Journal 12/2007; 1(2):120-1. · 1.66 Impact Factor
  • Gunnar Hillerdal, Göran Elmberger
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    ABSTRACT: Mesothelioma can occur in different variants, some of which are difficult or impossible to differentiate from sarcomas. There are scattered reports of sarcomatous mesotheliomas that have osteogenic properties. Here, we report a 57-year old man who presented with a mediastinal tumor containing scattered irregular calcifications with some scattered pleural thickening of the right pleura. Biopsy showed a sarcoma with bone formation. The man was born in the Turkish village of Karain, where the incidence of mesothelioma is extremely high, and a sarcomatous mesothelioma was therefore diagnosed. Since the tumor was pressing against the large vessels and heart, a debulking was performed, followed by Pemetrexed and Carboplatin treatment. However, the tumor grew rapidly and spread to the pleura, involved the heart, and the patient succumbed. This is to our knowledge the first report of a sarcomatous mesothelioma with bone formation from environmental exposure to mineral fibers.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2007; 2(10):983-4. · 4.55 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is associated with smoking but other etiological factors contribute. Chlamydia pneumoniae is an obligate intracellular bacterium causing both acute and chronic respiratory tract infections. Studies have revealed an association between chronic C. pneumoniae infection and COPD, asthma and lung cancer but there have been difficulties detecting C. pneumoniae in the bronchial tree. Cytospin slides prepared from bronchoalveolar lavage (BAL) fluid from 14 patients with COPD, 10 healthy smokers (S) and 7 non smokers (NS) were analyzed with a fluorescein isothiocyanate labeled monoclonal antibody to C. pneumoniae. Lung tissue from 24 patients with advanced emphysema who had undergone lung volume reduction surgery (LVRS) was examined with immunohistochemistry for C. pneumoniae. Archived serum samples for detection of specific C. pneumoniae antibodies by microimmunofluorescence were available for 30 of the BAL subjects and 11 of LVRS patients. C. pneumoniae elementary body like structures were found in 29% of cytospin specimens from COPD patients, 14% of NS and 10% of HS. C. pneumoniae was detected in lung tissue in 8%. COPD patients had higher titres of IgG and IgA than NS and S. There was no association between occurrence of C. pneumoniae in BAL fluid and antibody titres. In conclusion, the assays used for detection of C. pneumoniae in lung tissue are feasible, and could be adapted in adequately powered studies to further confirm an association between C. pneumoniae infection and COPD.
    International Journal of COPD 02/2007; 2(4):643-50.
  • Hirsh Koyi, Gunnar Hillerdal, Eva Brandén
    Journal of Thoracic Oncology - J THORAC ONCOL. 01/2007; 2.
  • Eva Brandén, Hirsh Koyi, Gunnar Hillerdal, Lotta Orre
    Journal of Thoracic Oncology - J THORAC ONCOL. 01/2007; 2.
  • Journal of Thoracic Oncology - J THORAC ONCOL. 01/2007; 2.
  • Source
    Gunnar Hillerdal, Lotta Orre
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    ABSTRACT: Three patients with very similar clinical symptoms, i.e. hemoptysis and coughing up of staples some time after volume-reducing surgery, are described. There was no deterioration in lung function, nor in the patient's well-being, which could be ascribed to the coughing up of the staples. Thus, staples can some time after volume reducing surgery erode out into the bronchi and be coughed up, often with some small amounts of blood. This has no clinical significance other than the disturbing symptoms. Possibly, the calf pericardium used as strenghtener of the suture lines will with time cause an immunological reaction, causing destruction of the foreign material and thereby dislodging the staples.
    Respiratory Medicine 03/2006; 100(2):371-3. · 2.59 Impact Factor
  • Gunnar Hillerdal, Anna Rask-Andersen
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    ABSTRACT: This study investigated the possibility of pleuropulmonary lesions, which can occur as rare but serious side effects of different ergot drugs, occurring more commonly in persons earlier exposed to asbestos. All reports of pleuropulmonary side effects of the ergot drugs used in Sweden in the Swedish side effect registry from 1985 to 2003 were studied. In addition, the literature was reviewed. In the registry, 47 men and 3 women were found. Of the men, 24 were exposed to asbestos, and 2 denied such exposure; 2 of the 3 women were exposed. In the literature, 111 patients were found--32 had confirmed exposure and 15 denied it. For most of the patients, it was not possible to determine exposure. Enough evidence exists to postulate that earlier asbestos exposure in combination with the intake of ergot drugs can cause pleuropulmonary lesions.
    Scandinavian journal of work, environment & health 01/2006; 31(6):459-64. · 3.78 Impact Factor
  • Lung Cancer. 01/2006; 54.
  • Lung Cancer. 01/2006; 54.
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    ABSTRACT: The aim of the present study was to investigate the frequencies of asbestos-related benign pleural diseases in villagers environmentally exposed to asbestos and the factors affecting these frequencies. A field-based, cross-sectional study was designed. In total, 991 villagers from 10 villages, randomly chosen from 67 villages with known use of asbestos-containing white soil in central Anatolia (Turkey), were investigated. The type of asbestos in the white soil was determined for each village, as well as air-borne fibre concentrations. The villagers were investigated with small-size chest roentgenograms and epidemiological features were recorded. The air-borne fibre levels were generally low. Despite this, pleural plaques were found in 14.4% of the villagers, 10.4% had diffuse pleural fibrosis and 0.4% asbestosis. The significant variables for plaques were age, sex, type of asbestos fibre, e.g. actinolite and tremolite, and exposure duration, while there was a negative relationship with cumulative exposure. The variables affecting diffuse pleural fibrosis were age, exposure duration and cumulative exposure. In conclusion, villagers exposed to environmental asbestos have high frequencies of pleural plaques and diffuse pleural fibrosis, similar to occupationally exposed asbestos cohorts. Different types of asbestos appear to result in different frequencies of pleural lesions.
    European Respiratory Journal 12/2005; 26(5):875-80. · 6.36 Impact Factor

Publication Stats

676 Citations
122 Downloads
3k Views
170.44 Total Impact Points

Institutions

  • 1999–2013
    • Karolinska Institutet
      • • Department of Laboratory Medicine
      • • Enheten för lungmedicin
      Solna, Stockholm, Sweden
  • 1997–2011
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2009
    • Hacettepe University
      Engüri, Ankara, Turkey
  • 1990–2009
    • Uppsala University
      • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
    • National Veterinary Institute, Sweden
      Uppsala, Uppsala, Sweden
  • 1990–2002
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden