Phase II trial of combined radiotherapy and daily low-dose cisplatin for inoperable, locally advanced non-small cell lung cancer (NSCLC).

With the use of cis-diamminedichloroplatinum(II), cisplatin, to enhance the effect of radiation a combined modality approach was designed to treat patients with inoperable, locally advanced NSCLC. The regimen consisted of radiation doses of 300 cGy for 4 days every week for 4 weeks with a 2 week split in between. Each radiation dose was followed by an i.v. injection of cisplatin 6 mg/m2 within 30 min. Hydration consisted on an oral fluid intake of 2 L only, enabling the patient to receive the treatment on an outpatient basis. Of 40 patients entered into the study, 37 were evaluable for toxicity and 33 for response. Overall response rate was 65% and complete response rate 22%. Median duration of local control was 7 months. The majority of all patients (76%) eventually progressed at the primary tumor site, while in 16 patients relapse occurred in distant sites first. Median duration of overall survival was 10.5 months, whereas that of complete responders was 29.5 months. Generally, acute side effects were transient and did not require discontinuation of treatment. One patient presented with thrombocytopenia 4 weeks after treatment had been finished. His death of cerebral bleeding was likely to be related with his therapy-resistant malignancy. Of late side effects three patients showed disabling symptoms consisting of uncontrollable pulmonary infections in the presence of tumor in two patients, one patient had radiation myelopathy and another experienced vertebral collapse with distal paresis. The combination of radiation and daily low-dose cisplatin is a tolerable treatment modality with most benefit for patients reaching a complete remission. Intensification of the regimen is being planned in those patients with inoperable, locally advanced squamous cell lung cancer to reach a complete remission.

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.

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Pulmonary function of patients with spontaneous pneumothorax in relation to the extent of emphysema-like changes.

The aim of the present study was to analyse pulmonary function parameters of patients with spontaneous pneumothorax (SP) in relation to the extent of emphysema-like changes (ELCs). Pulmonary function tests were performed in 85 patients with unilateral SP, 6 weeks after video-assisted thoracoscopy (VAT). In 63 patients, thoracic computer tomography (CT) was obtained. An ELCs score, based on findings of CT and VAT, was used to quantify ELCs, ranging from 0 (expressing no ELCs) to 3 (expressing extensive ELCs). Emphysema-like changes were detected during VAT in 74% of patients, of which 70% were considered larger than 2 cm. An ELCs score > or = 2 was found in 27 patients. Clinical characteristics of the patients grouped according to thoracoscopical findings and ELCs score did not differ, except for age. Patients with large ELCs were significantly older than patients without ELCs or small ELCs (P = 0.0009). In patients with large ELCs and ELCs score > or = 2, increased mean percentages of predicted total lung capacity and decreased diffusing capacity (KCO) were found. None of the patients exhibited all pulmonary function criteria of emphysema, in contrast to 43% of the patients with an ELCs score > or = 2. KCO was the only pulmonary function parameter which was decreased in smokers, especially in patients with large ELCs or ELCs score > or = 2. Static lung compliance (Cstat) was the only pulmonary function parameter which was increased in patients with recurrent SP. The authors concluded that KCO is related to smoking behaviour and ELCs in patients with SP. Cstat is the only parameter which is increased in patients with recurrent SP. The discrepancy between pulmonary function and macroscopical parenchymal changes could be explained by the fact that not all patients with SP are old enough at presentation to show all signs of emphysema with pulmonary function testing. On the other hand, it might be possible that ELCs in SP cause different pulmonary function abnormalities than in centriacinar or panacinar emphysema.

Magnetic resonance imaging vs palpation of cervical lymph node metastasis.

In a series of 100 patients with head and neck carcinoma, the preoperative histopathologic findings of palpation and magnetic resonance imaging were compared with regard to both laterality and lymph node level (I through V). The overall error for palpation in detecting affected sides was 32%. Gadolinium-enhanced magnetic resonance images reliably upgraded 60% of the clinically negative necks, the overall error of magnetic resonance imaging being 16%. However, for both modalities, the sensitivity per level was too low to allow for selective neck dissections in case of only one positive level. These findings show that apart from primary tumor grading, magnetic resonance imaging can improve the preoperative grading of cervical lymph nodes. In selected cases, this may change the treatment plan to a "wait-and-see" policy or a more conservative type of neck dissection.

Radioimmunotargeting in ovarian carcinoma patients with indium-111 labeled monoclonal antibody OV-TL 3 F(ab')2: pharmacokinetics, tissue distribution, and tumor imaging.

Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab')2 fragments of the murine monoclonal antibody OV-TL 3, labeled with 150 MBq Indium-111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t(1/2)}alpha = 1.4+/-0.8 h and t(1/2)}beta = 25.1+/-3.7 h, resulting in an optimal time period for immunoscintigraphy at 24-48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2-19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.

Severe acute lung injury induced by gemcitabine.

Gemcitabine is a nucleoside analog that is active in the treatment of various solid tumors. In general it is well tolerated and has few side effects. Pulmonary toxicity reported with gemcitabine use is usually mild and self-limiting. We present a case of severe pulmonary dysfunction after intravenous administration of a single dose of gemcitabine in a 58-year-old female patient with metastatic carcinoma of the pancreas. She developed tachypnea, marked hypoxemia, and an interstitial infiltrate on chest radiograph consistent with pulmonary edema, 4 days after receiving this drug. Diuretics and corticosteroids were beneficial in treating the acute respiratory failure. Pulmonary damage was completely resolved by means of clinical and radiological assessment. Because of the severity of this side effect, no further treatment with gemcitabine was given. Eventually, the patient died because of obstruction of the bowel due to progression of tumor growth. Publications concerning severe pulmonary toxicity due to gemcitabine are sparse. Pathophysiology and treatment are considered and a review of the literature is presented.

Disseminated aspergillosis after near-drowning.

We report a case of invasive pulmonary aspergillosis after near-drowning complicated by systemic disseminated disease to the heart, kidneys, left adrenal gland and brain. Detection of fungal micro-organisms in the sputum of near-drowning patients should be taken seriously.

Inclination of the temporomandibular joint eminence and anterior disc displacement.

The articular eminence angle of 179 temporomandibular joints (TMJ) with anterior disc displacement (ADD) in 179 patients was measured and compared with 200 left and 200 right joints of 400 young adults without TMJ dysfunction. A steeper inclination of the posterior slope of the articular eminence, with a mean difference compared to the control group of 14.5 degrees, was seen in joints with ADD. In the group of 179 joints with ADD of the TMJ, no difference was seen in the mean articular eminence angle between joints with an ADD with reduction, and an ADD without reduction, between conservatively or surgically treated joints, or between joints with different presumed causes of ADD.

CT and nuclear medicine imaging in vertebral metastases.

Three cases are presented to illustrate the value of CT in elucidating the diagnosis in cancer patients presenting with complaints that are clinically highly suspicious for osseous metastases, where isotope bone imaging and conventional radiography failed to confirm the clinician's suspicion.

[Diagnosis of pneumothorax not improved by additional roentgen pictures of the thorax in the expiration phase]. / Diagnostiek van pneumothorax niet gediend door aanvullende röntgenopname van de thorax in expiratiestand.

OBJECTIVE: To evaluate whether an expiratory chest roentgenogram adds anything to the results obtained by a standard inspiratory chest roentgenogram in patients with a pneumothorax. DESIGN: Retrospective analysis and blinded re-evaluation of the radiographs. SETTING: Free University Hospital, Amsterdam. METHOD: Of 59 patients with a proven pneumothorax the chest roentgenograms at the time of the pneumothorax (54 inspiratory and 46 expiratory roentgenograms) were evaluated independently by 4 investigators in random order, as were 28 roentgenograms of the same patients made on different occasions. RESULTS: On all expiratory chest roentgenograms the pneumothorax was seen, of the 54 inspiratory ones two investigators missed one very small apical pneumothorax. All 28 control roentgenograms were scored correctly. No reliable additional information was obtained from the expiratory X-rays with regard to the cause of the pneumothorax. CONCLUSION: Expiratory chest roentgenograms are not indicated as a routine investigation for patients in whom pneumothorax is suspected.

[The usefulness of thoracic computerized tomography in patients in an intensive care unit]. / Het nut van computertomografie van de thorax bij patiënten op een intensive care-afdeling.

Performing thoracic CT scanning in critically ill patients can be cumbersome and may have detrimental effects on the condition of the patient. We retrospectively analysed the clinical data of 46 patients who were examined over a period of 4.5 years. The thoracic CT scanning was judged useful in 40 patients (87%) and beneficial for 23 (50%) of these. The principal indications for the investigation are: suspected pulmonary abscess, suspected mediastinitis, precise localisation of an intrathoracic lesion prior to surgery, difficulty in the evaluation of the pulmonary parenchyma in patients with deforming thoracic kyphoscoliosis, suspected trapped pleural fluid and a suspected thoracic focus of sepsis. Transport had no detrimental effects on any of the patients. If the decision to undertake CT scanning is arrived at jointly by the radiologist and intensive care physicians, CT scanning is useful and can be performed safely if transport is undertaken by an experienced team.

[The diagnostic value of immunoscintigraphy using the monoclonal antibody OV-TL3 in patients with ovarian carcinoma]. / De diagnostische waarde van de immunoscintigrafie met het monoklonale antilichaam OV-TL3 bij patiënten met ovariumcarcinoom.

Immunoscintigraphy, using radiolabeled monoclonal antibodies directed against tumor associated antigens, is a relatively new method for the detection of tumour localizations. The diagnostic accuracy of immunoscintigraphy was compared with computer tomography, magnetic resonance imaging, ultrasound, physical examination, and the CA 125 serum assay in patients suspected of having primary or recurrent ovarian cancer. One mg of the murine monoclonal antibody OV-TL3 F(ab')2 was labeled with 4 mCi 111Indium and administered intravenously to 28 patients. No adverse reactions were noted. Twenty patients underwent extensive explorative laparotomy 3 to 8 (median 4 days) days after injection of the immunoconjugate, allowing a histopathological verification of the actual tumour status of each patient. The sensitivity of immunoscintigraphy for the detection of ovarian cancer was at least equal to that of the other diagnostic methods. However, with immunoscintigraphy more tumour localizations were identified.

[Diagnosis of laryngeal carcinoma using proton spin resonance tomography]. / Diagnostiek van larynxcarcinoom met kernspinresonantie-tomografie.

Seventy-eight patients were investigated by magnetic resonance (MR) imaging using optimal scan parameters and a surface coil. Forty-two patients were also examined by computer tomography (CT). Sixteen patients underwent laryngectomy. MR imaging of cancerous tissue in the larynx, and particularly of non-invaded and invaded cartilages, was examined by comparing MR images with sliced surgical specimens. Pre-operative CT and MRI findings were evaluated by comparing them with postoperative histopathological findings. MR T1-weighted images demonstrate localisation and extent of cancerous tissue. With combined use of T1-weighted and proton-density images MR imaging is superior to CT for showing cartilage invasion. Unfortunately, gross movement artifacts, which resulted in non-diagnostic images, occurred in 16% of the examinations.

[Added value of positron emission tomography with fluoro-18-deoxyglucose as the tracer (FDG-PET) in clinical problem cases in oncology]. / Meerwaarde van positronemissietomografie met als tracer fluor-18-deoxyglucose (FDG-PET) bij klinische probleemgevallen in de oncologie.

Positron emission tomography with fluoro-18-deoxyglucose as tracer molecule (FDG-PET) is a relatively new imaging technique used in oncology to study tumour metabolism in vivo. Both qualitative and quantitative data obtained by PET provide unique information to the clinician and may guide the therapeutic approach in selected patients, where conventional diagnostic tests like CT or MRI yield equivocal results. According to the experience obtained in the Vrije Universiteit Medical Centre in Amsterdam, the additional value of FDG-PET can be explained by the sensitivity and the specificity of the technique, combined with the visualization of the whole body. FDG-PET may reveal metastases and tumour tissue may be differentiated from scar tissue and necrosis. PET is expensive and its effects on patient outcome has yet to be established.