Fluorescein-aided confocal laser endomicroscopy of the lung.

BACKGROUND: There are only few reports about confocal laser endomicroscopy (CLE) for pulmonary imaging. In these studies, in contrast to gastrointestinal endoscopy, CLE was performed without fluorescein. OBJECTIVES: The aim of the present study was to evaluate the value of fluorescein usage for CLE of the lung. METHODS: Fluorescein-aided CLE was performed in 15 consecutively recruited patients and in 4 young healthy volunteers with a miniprobe during flexible bronchoscopy. Before and after intravenous administration of fluorescein, central airways and alveolar structures were evaluated. RESULTS: Fluorescein administration did not permit imaging of epithelial cells in the central airways. In the lung periphery, alveolar walls and partially macrophages could be seen in native imaging, as expected. After administration of fluorescein, alveoli were almost filled with foam in areas with normal lung tissue. The origin of this foam was shown to be artificial. Furthermore, in patients with pathologies of the lung parenchyma, dark neoplastic and inflammatory cells adjacent to the alveolar walls were identified. No relevant side effects of fluorescein administration could be observed. CONCLUSIONS: Fluorescein-aided CLE of the lung appeared to be safe and well tolerated. While the lack of staining of cells in the central airways was a major limitation, it permitted analysis of the lung interstitium and alveolar space and thus emerges as a new approach for the in vivo analysis of interstitial lung diseases.

Percutaneous radiofrequency ablation of liver tumors using multiple saline-perfused electrodes.

PURPOSE: Radiofrequency ablation (RFA) with multiple saline-perfused electrodes is a minimally invasive alternative to archive large coagulation zones. Few long-term results have been published so far. This is a report of our long-term experience using multiple saline-perfused electrodes for the treatment of malignant hepatic tumors. MATERIALS AND METHODS: Thirty-eight patients with biopsy-proven hepatocellular carcinoma (HCC) or liver metastases of colorectal cancer (CRC) (17 CRC, 21 HCC) with a total of 56 tumors (26 CRC, 30 HCC) were treated with the Integra HiTT 106 RF generator using multiple saline-perfused electrodes. Mean size was 42 mm for HCC and 36 mm for CRC. Follow-up examinations took place after 2 days and 1, 3, 6, and 9 months after RFA and every 6 months thereafter. RESULTS: We performed 2.6 (2.7 CRC, 2.4 HCC) sessions per patient. Major complications occurred in 2% of patients. Ninety-two percent (35/38) were treated technically successfully. Local tumor progression was found in 8 patients out of 35 (22% overall, 21% HCC, 25% CRC). For HCC, 43% of patients suffered distant intrahepatic recurrence. One- and two-year survival for HCC patients was 71% and 58%. (Child-Pugh status A, one- and two-year survival was 90% and 80%; Child status B, 35% and 18%). For CRC, 11 of 17 (65%) patients suffered distant intrahepatic recurrence. One- and two-year survival for CRC patients was 94% and 86%. CONCLUSIONS: RFA using multiple saline-perfused electrodes shows results in the treatment of liver tumors comparable with other established ablation techniques.

Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits.

Radio-frequency ablation (RFA) is used as a minimally invasive treatment for inoperable hepatic tumors. Immunological reactions secondary to RFA may play a role in the observed tumor control. In our study, the VX2 carcinoma was implanted into the liver of rabbits. After 3 weeks, tumors were treated with RFA or were left untreated. Peripheral blood lymphocytes were harvested before tumor implantation, 2 weeks postoperatively and at 2-week intervals thereafter. T cells were stimulated with lysates of either tumor tissue or nontumorous liver loaded on autologous antigen-presenting cells and their stimulation index was determined by [(3)H]thymidine incorporation. A 3-fold increase over background or controls was considered significant. Stimulation with phytohemagglutinin served as a positive control. The animals were necropsied, and liver and tumor tissue were analyzed immunohistologically for T-cell infiltration. T cells from tumor-bearing (n = 9) and RFA-treated (n = 11) animals were investigated in a follow-up study. The mean postoperative observation was 45 days. All of the 11 RFA-treated animals exhibited circulating T cells activated specifically toward tumor antigens throughout the observation period, which was accompanied by dense T-cell infiltration. In contrast, T cells of untreated tumor-bearing rabbits showed no reaction and only sparse T cell infiltration. We concluded that RFA induces a tumor-specific T-cell reaction in the otherwise unreactive tumor-bearing host, apparently overcoming immune tolerance and leading to the presentation of otherwise cryptic tumor antigens. Therefore, in addition to destroying tumor tissue, RFA induces an immune response against tumor antigens that may be exploited in multimodal antitumor strategies.

2-aroylindoles, a novel class of potent, orally active small molecule tubulin inhibitors.

2-Aroylindoles with 5-methoxy-1H-2-indolyl-phenylmethanone (D-64131) as the lead structure were discovered as a new class of synthetic, small molecule tubulin inhibitors. By competitively binding with [(3)H]colchicine to alphabeta-tubulin and inhibiting microtubule formation, cycling cells were arrested in the G(2)-M phase of the cell division cycle. The proliferation of tumor cells from 12 of 14 different organs and tissues was inhibited with mean IC(50)s of 62 nM and 24 nM by D-64131 and D-68144, respectively, comparable with the potency of paclitaxel with mean IC(50) of 10 nM. By measuring the cytotoxicity in a human colon carcinoma cell model with ectopic ecdysone-inducible expression of the cyclin-dependent kinase inhibitor p21(WAF1), specificity toward cycling cells was demonstrated. In contrast to microtubule inhibitors from natural sources, 2-aroylindoles did not alter the polymerization-dependent GTPase activity of beta-tubulin and are not substrates of the multidrug resistance/multidrug resistance protein efflux pump. No cross-resistance toward cell lines with multidrug resistance/multidrug resistance protein independent resistance phenotypes became evident. In animal studies, no signs of systemic toxicity were observed after p.o. dosages of up to 400 mg/kg of D-64131. In xenograft experiments with the human amelanoic melanoma MEXF 989, D-64131 was highly active with treatment resulting in a growth delay of 23.4 days at 400 mg/kg. Therefore, D-64131 and analogues have the potential to be developed for cancer therapy, replacing or supplementing standard therapy regimens with tubulin-targeting drugs from natural sources.

Hepatic transit time of an echo enhancer: an indicator of metastatic spread to the liver.

OBJECTIVE: Can sonographic measurements of the transit time of an echo enhancer from the hepatic artery to the hepatic vein discriminate between patients with and without liver metastases? METHOD: The hepatic transit time (hepatic artery to hepatic vein delay) of an echo enhancer (Optison) was measured in pulse inversion mode on the basis of time intensity curves (TIC) in patients with gastrointestinal tumours with proven liver metastases and in patients without liver metastases. RESULTS: Sixty-four patients (46 males, 18 females, mean age 61 +/- 13 years) were admitted to the study. Fourteen patients had metastatic growth in the liver with a primary tumour in situ (group A). Fourteen patients had liver metastases following primary tumour resection (group B). Twenty-eight patients had a known primary tumour but no liver metastases (group C), and eight patients had neither liver symptoms nor a primary tumour (group D). The mean hepatic transit time in patients with liver metastases was 6.6 +/- 1.8 s in group A and 6.7 +/- 1.7 s in group B, whereas in patients without liver metastases it was significantly longer; namely, 15.7 +/- 4.4 s in group C and 15.0 +/- 2.0 s in group D (P < 0.001). The transit times in all patients with liver metastases were < or = 10 s, while in all patients without metastases except for four the times were > or = 12 s and one of the four had already developed liver metastases on early follow-up. CONCLUSIONS: Measurement of the hepatic transit time permits discrimination of patients with and without liver metastases.

Public spirometry for primary prevention of COPD.

BACKGROUND: The most effective action for primary prevention of chronic obstructive lung disease is smoking cessation early enough. In secondary prevention, smokers with airway obstruction were more likely to quit smoking. The aim of this study was to evaluate the impact of a public spirometry on smoking habits in terms of primary prevention. METHODS: Spirometry with its medical analysis was offered to visitors of a local public event called 'Lange Nacht der Wissenschaften' ('Long night of sciences'). The impact of results on smoking habits was evaluated in all smokers with an anonymized questionnaire afterwards. RESULTS: Two hundred fifty-seven people with the median age of 30 years (interquartile range 22-46) were examined. Out of 44 current smokers (17.1%), only two individuals showed a prebronchodilator FEV1/forced vital capacity-value <0.7. Fourteen smokers stated to have an increased motivation to quit smoking whereas 28 smokers declared that their motivation to quit smoking was independent of spirometry result. These smokers were significantly younger (median age 28 vs. 40 years, P = 0.025) without differences in spirometry results or smoking habits. CONCLUSION: In an unselected population with a high amount of younger adults, normal spirometry did not show a short-term benefit for primary prevention of chronic obstructive lung disease in terms of increasing motivation to quit smoking.

[Pulsed radiofrequency ablation using perfused needle applicators in an in vitro trial on bovine liver]. / Getaktete Dreifachapplikation mit perfundierten Nadelapplikatoren bei Radiofrequenzablation: In-vitro-Versuch an der Rinderleber.

Intermittent energy application seems to have positive effects in achieving necrotic zones. We analyzed different pulse periods (PPs) to optimize this method. A radiofrequency alternating current was delivered via a triple-needle applicator (3 cm distance of each needle) introduced into freshly procured bovine liver. The open applicator system was constantly perfused with physiological NaCl solution (3×80 ml/h, power output was constant 90 W). Radiofrequency current was fed to the individual needle in turn of varying PPs (1, 2, 5, and 7 s) over 15 min. Each experimental run comprised a total of 30 applications and temperature was recorded over time. The largest necrotic diameters were found at PP 1 s (relevant: shortest axial diameter/D in the center of the lesion: 9.27 cm, SD±0.97 cm) (PP 2 s D=8.65 cm, SD±0.95 cm, p=0.021; PP 5 s D=8.35 cm, SD±0.95 cm, p=0.001; PP 7 s D=8.18 cm, SD±0.79 cm, p=0.0001). Neither doubling the perfusion rate nor raising the concentration of the perfusion liquid led at PP 1 s to increased necrotic diameters (p=0.82). Our study shows that reducing the PP to 1 s of an open perfused intermittent radiofrequency ablation system produces significantly larger coagulation volumes in explanted liver tissue reaching necrotic diameters over 9 cm. Neither doubling perfusion rates nor higher concentrated perfusion liquid increase necrotic diameters.

Percutaneous US-guided radiofrequency ablation with perfused needle applicators: improved survival with the VX2 tumor model in rabbits.

PURPOSE: To evaluate survival, metastases, tumor necrosis, and prediction of local recurrence after percutaneous ultrasonographically (US) guided radiofrequency (RF) thermal ablation with electrodes perfused continuously with isotonic saline. MATERIALS AND METHODS: VX2 liver tumors were implanted in 31 rabbits according to a standardized protocol. After 21 days, 16 animals were treated percutaneously with RF ablation. Four animals died of complications related to anesthesia, and 12 animals were evaluated. All animals were followed for 110 days and monitored with computed tomography (CT) and US at 1, 7, and 30 days. A control group of 15 animals did not receive treatment. Autopsy was performed at the end of scheduled follow-up or immediately after death. For survival analysis, the Kaplan-Meier method was used; for nominal data, the Fisher exact test was used. RESULTS: In comparison to controls, animals in the treatment group showed significantly prolonged survival (P <.001). Eight of 12 animals (67%) treated with RF ablation survived to 110 days, while none of the controls did so. Metastases developed in all controls (100%) and in eight of 12 treated animals (67%) (P =.001). In comparison with controls, animals that developed metastases despite treatment also showed significantly prolonged survival (P =.02). Local recurrence was observed in three of 12 animals (25%) in the treatment group. CT and US performed 1 week after treatment did not allow prediction of local recurrence. CONCLUSION: RF ablation of liver tumors with perfused needle applicators prolongs survival in the VX2 rabbit liver tumor model, regardless of whether complete remission is achieved. In comparison with controls, RF ablation results in a lower frequency of metastases.