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

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC.

Esophageal symptoms with negative influence on social life. Radiographic and manometric findings.

PURPOSE: To correlate the functional changes of the esophagus determined by manometry and radiography using bread and barium with the severity of esophageal symptoms. MATERIAL AND METHODS: Fifty-seven patients, mean age 44.4 years, suspected of primary esophageal motility disorders underwent simultaneous video-radiography and manometry. Based on interviews the patients were divided into subgroups according to predominant symptom - gastro-esophageal reflux symptoms, dysphagia, or chest pain - and to severity of symptoms, i.e., symptoms with negative or no influence on daily life. The manometric diagnosis and esophageal emptying were based on both liquid and solid swallows. RESULTS: There was significant difference in the incidence of esophageal dysmotility disorders both globally and in the subgroup of patients with dysphagia between patients with and those without severe symptoms, but only after solid swallows. CONCLUSION: We suggest employment of bread in esophageal function tests to improve the correlation between symptomatology and positive diagnostics findings.

Outpatient treatment with subcutaneous histamine dihydrochloride in combination with interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma: results of an open single-armed multicentre phase II study.

OBJECTIVES: Histamine inhibits formation and release of monocyte/macrophage-derived reactive oxygen metabolites and thereby protects natural killer (NK) and T cells against oxidative inhibition. Efficacy and safety of histamine, when given in combination with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), were evaluated in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Forty-eight mRCC patients were included. The self-administered, outpatient regimen included IFN-alpha, 3 MIU s.c., once daily for 1 week, followed by up to nine 4 week cycles of IFN-alpha, 3 MIU s.c., days 1-7, weeks 1-4; interleukin-2, 2.4 MIU/m2 s.c., b.i.d., days 1-5, weeks 1 and 2; and histamine dihydrochloride, 1 mg s.c., b.i.d. days 1-5, weeks 1-4. RESULTS: Forty-six patients were eligible. Forty-two patients were evaluable for response with four partial responses (9% of eligible patients, 10% of evaluable patients). Fifteen patients (36%) had stable disease. After subsequent surgery of residual tumours, three patients (7%) had no evidence of disease at 14+, 21+ and 21+ months. Median survival time for all patients was 16.3 months. One grade 4 toxicity (thrombocytopenia) was observed. Most frequent grade 3 toxicities were fatigue/malaise (26%), dyspnoe (11%), nausea (9%) and stomatitis (9%). Four patients discontinued due to treatment-related toxicity. There were no treatment-related deaths. CONCLUSIONS: The present combination of histamine with IL-2 and IFN-alpha. as self-administered outpatient therapy is a safe and well-tolerated regimen. However, histamine does not appear to add efficacy with respect to response in this low-dose schedule of IL-2 and IFN-alpha. Whether histamine might improve efficacy with higher doses of IL-2 and IFN-alpha requires further investigation.

Bread and barium. Diagnostic value in patients with suspected primary esophageal motility disorders.

PURPOSE: To evaluate the significance of bread and barium studies as a diagnostic tool as well as a supplement to manometric investigation of the esophagus in patients with suspected esophageal motility disorders. MATERIAL AND METHODS: Eighty-nine patients suspected for primary esophageal motility disorders were examined. All patients were interviewed before the investigation to determine the prevalence of symptoms like heartburn, chest pain, and dysphagia. The patients underwent simultaneous roentgenologic and manometric investigations in the supine position during wet and solid barium swallow, and during continuous drinking, followed by investigation for gastroesophageal reflux (GER). The manometric examination was performed with triple-lumen catheters connected to a hydraulic capillary infusion system and external transducers. RESULTS: All patients with normal esophageal clearing (n=31) had normal manometry. Patients with delayed esophageal clearing (n=58) required manometry for identifying concommittant motility disorders; achalasia and diffuse esophageal spasms were found only in patients with delayed liquid and solid emptying. GER and/or esophageal rings was demonstrated in 31 patients. CONCLUSION: We suggest bread and barium as the first diagnostic step in patients with clinical suspicion of primary esophageal motility disorders.