Dynamic contrast-enhanced CT in suspected lung cancer: quantitative results.

OBJECTIVES: To examine whether dynamic contrast-enhanced CT (DCE-CT) could be used to characterise and safely distinguish between malignant and benign lung tumours in patients with suspected lung cancer. METHODS: Using a quantitative approach to DCE-CT, two separate sets of regions of interest (ROIs) in tissues were placed in each tumour: large ROIs over the entire tumour and small ROIs over the maximally perfused parts of the tumour. Using mathematical modelling techniques and dedicated perfusion software, this yielded a plethora of results. RESULTS: First, because of their non-normal distribution, DCE-CT measurements must be analysed using log scale data transformation. Second, there were highly significant differences between large ROI and small ROI measurements (p<0.001). Thus, the ROI method used in a given study should always be specified in advance. Third, neither quantitative parameters (blood flow and blood volume) nor semi-quantitative parameters (peak enhancement) could be used to distinguish between malignant and benign tumours. This was irrespective of the method of quantification used for large ROIs (0.13

Limited value of 99mTc depreotide single photon emission CT compared with CT for the evaluation of pulmonary lesions.

OBJECTIVES: A contrast-enhanced multidetector CT (MDCT) scan is the first choice examination when evaluating patients with suspected lung cancer. However, while the clinical focus is on CT, research focus is on molecular biological methods whereby radiolabelled pharmaceuticals are injected into participants and target malignant lung tumours. We examined whether a contrast-enhanced MDCT scan supplied with an additional non-contrast enhanced high-resolution CT scan, or a newer but more expensive (99m)Tc depreotide single photon emission CT (SPECT) scan, was the better first-choice examination for the work-up of pulmonary lesions. Furthermore, we examined whether a (99m)Tc depreotide SPECT scan was an appropriate second-choice examination for patients with indeterminate lesions. METHODS: 140 participants were included in the analysis. CT images were given a malignancy potential rating of 1, 2 or 3 with higher rating being indicative of disease. (99m)Tc depreotide SPECT images were graded either positive or negative. Histopathology and CT follow-up were used as reference standard. Sensitivity, specificity and diagnostic accuracy were calculated. RESULTS: Overall sensitivity, specificity and diagnostic accuracy of CT were 97%, 30% and 84%, respectively. Overall sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 94%, 58% and 76%, respectively. For indeterminate lesions sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 71%, 68% and 69%, respectively. CONCLUSION: Both CT and (99m)Tc depreotide SPECT made valuable contributions to the evaluation of pulmonary lesions. (99m)Tc depreotide SPECT results were not superior to CT results and did not contribute further to the diagnostic work-up. Regarding indeterminate lesions,( 99m)Tc depreotide SPECT sensitivity was too low.

Imaging follow-up of RF ablation of lung tumours.

Imaging is important in the decision-making process of how to treat a lung tumour, which ideally should be a multi-disciplinary team decision. Imaging is important during radiofrequency ablation (RFA) treatment with regard to optimal placement of the electrode, the immediate post-treatment criteria and very early detection of complications of the procedure. Imaging is very important in the treatment follow-up. In lung RFA, as in many other interventional procedures, the traditional morphological imaging techniques to evaluate treatment response have difficulties and functional imaging techniques may potentially be more useful. However, larger studies showing this impact have not yet been performed.

Contrast-enhanced ultrasound in oncology.

In patients with known malignant disease, 51% of liver lesions less than 1.5 cm turn out to be benign. Whether the probability of malignancy is high or low, further investigations are often necessary to definitely exclude malignancy. Contrast-enhanced ultrasonography has a prominent role in lesion characterization with a diagnostic accuracy comparable with computed tomography and magnetic resonance imaging. Anti-angiogenic treatment is common in most oncological institutions and the response evaluation is a new challenge with a research focus on the change in tumour vasculature and perfusion. In planning biopsies, CEUS can identify necrotic and viable areas of tumours and improve the diagnostic accuracy.

PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer.

BACKGROUND: We have previously developed (11)C-erlotinib as a new positron emission tomography (PET) tracer and shown that it accumulates in epidermal growth factor receptor (EGFR)-positive lung cancer xenografts in mice. Here, we present a study in patients with non-small cell lung cancer (NSCLC) investigating the feasibility of (11)C-erlotinib PET as a potential method for the identification of lung tumours accumulating erlotinib. METHODS: Thirteen patients with NSCLC destined for erlotinib treatment were examined by contrast-enhanced computed tomography (CT), (11)C-erlotinib PET/low-dose CT and (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/low-dose CT before start of the erlotinib treatment. After 12 weeks treatment, they were examined by (18)F-FDG PET/contrast-enhanced CT for the assessment of clinical response. RESULTS: Of the 13 patients included, 4 accumulated (11)C-erlotinib in one or more of their lung tumours or lymph-node metastases. Moreover, (11)C-erlotinib PET/CT identified lesions that were not visible on (18)F-FDG PET/CT. Of the four patients with accumulation of (11)C-erlotinib, one died before follow-up, whereas the other three showed a positive response to erlotinib treatment. Three of the nine patients with no accumulation died before follow-up, four showed progressive disease while two had stable disease after 12 weeks of treatment. CONCLUSION: Our data show a potential for (11)C-erlotinib PET/CT for visualizing NSCLC lung tumours, including lymph nodes not identified by (18)F-FDG PET/CT. Large clinical studies are now needed to explore to which extent pre-treatment (11)C-erlotinib PET/CT can predict erlotinib treatment response.

Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial.

Histamine (HDC) inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer (NK) and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). We have explored this potential mechanism clinically in two randomised phase II trials in metastatic renal cell carcinoma (mRCC). In parallel with the clinical trial in Denmark (n=63), we obtained serial blood samples and tumour biopsies searching for a potential histamine effect in situ. At baseline and on-treatment weeks 3 and 8, we monitored the 'good guys' (i.e. NK and T cells) and 'bad guys' (i.e. monocytes/macrophages and neutrophils) simultaneously in blood (n=59) and tumour tissue (n=44). Patients with high number of monocytes and neutrophils in peripheral blood had very poor survival, with apparently no benefit from either IL-2 alone or IL-2/HDC treatment. Blood monocytes (r=-0.36, P=0.01) and neutrophils (r=-0.46, P=0.001) were negatively correlated with cytotoxicity, whereas blood NK cells were positively correlated with cytotoxicity (r=0.39, P=0.002). Treatment with IL-2 alone resulted in a significantly higher number of circulating monocytes (P=0.037) and intratumoral macrophages (P=0.005) compared with baseline. In contrast, IL-2/HDC resulted in an unchanged number of circulating monocytes and intratumoral macrophages, and in addition, a significantly increased number of intratumoral CD56(+) NK cells (P=0.008) and CD8(+) T cells (P=0.019) compared with baseline. The study provides evidence that circulating monocytes and neutrophils are powerful negative prognostic factors for IL-2-based immunotherapy and establishes a biological rationale for the potential use of histamine in conjunction with IL-2 in mRCC.

In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma.

The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN-alpha-based immunotherapy in 34 patients and repeated after 5 weeks in 25 patients. Tumour proliferation was assessed by use of the anti-Ki-67 antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. Ki-67 labelling index (LI) at baseline was median 13.6% (range 1.2-85.0) and median 10.6% (range 1.3-48.6%) at week 5 with a median overall decline of 15.2% (range -95 to +258%) from baseline to week 5. There was no difference between responding and nonresponding patients. Ki-67 LI at week 5 was significantly correlated to survival. Thus, median survival of patients with Ki-67 LI 10.6% (P=0.016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival.

Anti-CD4 monoclonal antibody treatment combined with total lymphoid irradiation and cyclosporin A in hamster-to-rat cardiac transplantation. Analysis of lymphocyte subsets and anti-donor xenoantibodies.

Combined treatment with total lymphoid irradiation and cyclosporin A results in prolonged graft survival in concordant xenogeneic cardiac transplantation, but reproducible long-term graft acceptance has proved to be difficult. Anti-CD4 monoclonal antibody treatment has been successful in inhibiting heart graft rejection in allogeneic models. Used as monotherapy in a concordant xenogeneic model for pancreatic islet transplantation, prolonged graft survival has been reported; however, no beneficial effect on primarily vascularized heart grafts was noted. The object of this investigation was to combine these treatment strategies with respect to reproducible long-term hamster heart graft survival in rats, to monitor the effect on lymphocyte subpopulations, and to determine possible anti-donor antibody formation correlated to time of rejection. Graft survival after combined preoperative total lymphoid irradiation and postoperative cyclosporin A + anti-CD4 monoclonal antibody treatment was prolonged from 14 to > 100 days (compared to spontaneous graft survival of three to four days), with long-term graft function in four of 19 recipients. Total white blood counts in the postoperative course were characterized by an unproportional increase of Ig+ cells and an incomplete recovery of CD4+ cells. Flow-cytometric analysis of anti-donor antibodies showed low levels of preformed antibodies and increasing amounts of strain-, but not donor-specific antibodies, correlated to the time of rejection. Long-term survivors with functioning grafts at the time of sacrifice had an initially moderate antibody increase with subsequent decrease to baseline levels. Our results indicate that total lymphoid irradiation combined with cyclosporin A and anti-CD4 monoclonal antibodies can prolong graft survival significantly in concordant hamster-to-rat cardiac xenotransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Asymptomatic benign mediastinal teratoma]. / Asymptomatisk benignt mediastinalt teratom.

A case of asymptomatic benign mediastinal teratoma is presented. The necessity for definite diagnosis of mediastinal tumours is stressed together with the need for conferences involving several specialties.

Arachnoid cyst with complicating intracystic and subdural haemorrhage.

Intracranial arachnoid cysts are usually non-symptomatic. Intracystic and subdural haematomas induced by even minor head injury may turn an asymptomatic AC into a symptomatic one, necessitating surgical treatment. We present a case of a previous asymptomatic AC, spontaneously complicated with subdural hygroma and development of intracystic and subdural haematoma. Clinical follow-up and control CT regime of patients with AC are recommended.

Hope for successful xenografting by immunosuppression with monoclonal antibody against CD4, total lymphoid irradiation and cyclosporine. Six months' survival of hamster heart transplanted into rat.

Hamster hearts were transplanted to rats, and the effects of combinations of total lymphoid irradiation (TLI), cyclophosphamide, cyclosporine A (CyA) and monoclonal antibodies (MAB) were investigated. Controls not immunosuppressed rejected their xenograft in 3 to 5 days, while combination immunosuppression including MABs against CD4 or IL-2-receptors extended graft survival significantly. In one case, the graft was still functioning 180 days after transplantation, which is the longest survival seen in this model. The use of specific MABs may open a new era for both xeno- and allo-transplantation.

Posterior transsphincteric rectotomy. Indications and safety.

This study intends to make the transsphincteric approach to the rectum more well known, mainly because of the increasing number of small carcinomas and adenomas being detected by endoscopy following screening for occult blood. Thirty patients had rectotomy from 1983 to 1987. Curative surgery was performed on 15, whereas adenomas were excised in 11. Other indications were palliative excision, rectovaginal fistula, and postsurgical bleeding. Two patients had had previous transversostomies and a covering colostomy was done in one. Complications included wound infection in four and rectal fistula in four. Transversostomy became necessary in three. All colostomies were closed later and the mortality was zero. All preserved anal continence for solid and fluid feces, whereas three suffered from flatulence during a follow-up period from one to 46 months. The approach allows surgery in the upper part of the lower third of the rectum and the midrectum with a low mortality and complication rate, and should be preferred over major surgery in selected patients.