MR-guided laser-induced thermotherapy in recurrent extrahepatic abdominal tumors.

The aim of this study was to evaluate the feasibility of MR-guided laser-induced thermotherapy (LITT) for treatment of recurrent extrahepatic abdominal tumors. In 11 patients (6 women and 5 men; mean age 53 years, age range 29-67 years) with 14 lesions the following tumors were treated in this study: paravertebral recurrence of hypernephroma (n=1); recurrence of uterus carcinoma (n=1); recurrence of chondrosarcoma of the pubic bone (n=1); presacral recurrence of rectal carcinoma (n=1); recurrent anal cancer (n=1); metastases in the abdominal wall (n=1); and lymph node metastases from colorectal cancer (n=8). A total of 27 laser applications were performed. A fast low-angle shot 2D sequence (TR/TE/flip angle=102 ms/8 ms/70 degrees ) was used for nearly real-time monitoring during treatment. All patients had no other treatment option. Seventeen LITT sessions were performed using a conventional laser system with a mean laser power of 5.2 W (range 4.5-5.7 W), and 10 LITT session were performed using a power laser system with a mean laser power of 28.0 W. In 10 lesions total destruction could be achieved. In the remaining recurrent tumors, significant reduction of tumor volume by 60-80% was obtained. All patients tolerated the procedure well under local anesthesia. No complications occurred during treatment. Laser-induced thermotherapy is a practicable, minimally invasive, well-tolerated technique that can produce large areas of necrosis within recurrent tumors, substantially reducing active tumor volume if not resulting in outright destruction of tumor.

[Transarterial chemoembolization in hepatocellular carcinomas: technique, indications, results]. / Transarterielle Chemoembolisation bei hepatozellulären Karzinomen: Technik, Indikationsstellung, Ergebnisse.

BACKGROUND: At time of diagnosis 80% of the patients with hepatocellular carcinoma (HCC) could not be treated with surgical treatments, so that transarterial chemoembolization (TACE) was used as an neoadjuvant or palliative treatment modality. MATERIAL AND METHODS: 60 patients were treated with 217 TACE courses, in the mean 3.6 TACE treatments per patient with an 4 week interval. TACE was performed with a dispersion of lipiodol, mitomycin C and spherex. 11 patients (18.3%) were treated in a neoadjuvant protocol with successful ablation. Lipiodol retention and size of the tumors were evaluated by CT and MRI. RESULTS: 60 patients were successful treated with TACE. After treatment a primary high lipiodol retention was displayed and in 68 (63.3%) patients a reduction of the tumor size and in 11 (20%) patients a reduction of tumor growth rate was noted. The 1 year survival rate was 59%. After response to TACE and reducing the tumor size 11 patients could be treated with MR-guided LITT 4 to 6 weeks post embolization. CONCLUSION: Chemoembolization is a minimal invasive and outpatient treatment protocol for HCC. TACE might be indicated as a palliative treatment to control the diseased liver. If repeated TACE alters the size and structure of primary unresectable HCC TACE expands the indication for MR-guided LITT.

[Oligonodular hepatocellular carcinoma (HCC): MR-controlled laser-induced thermotherapy]. / Oligonoduläres hepatozelluläres Karzinom (HCC): MR-gesteuerte laserinduzierte Thermotherapie (LITT).

PURPOSE: To prospectively evaluate the therapeutic potential of MR-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. MATERIAL AND METHODS: 39 patients with 61 intrahepatic lesions were treated with LITT. The Nd:YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. RESULTS: All patients tolerated the procedure well under local anesthesia. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application, larger lesions were treated simultaneous multiapplication. In 97.5% we achieved a complete necrosis of the tumor and a 5 mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival was 4.4 years (95% CI: 3.6-5.2 years) after the time of diagnoses of the HCC (Kaplan-Meier-method). CONCLUSION: In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure with a high tumor control rate and better survival data.

Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases.

BACKGROUND: Many primary tumors may cause liver metastases, which are generally treated with surgical resection and/or chemotherapy. After resection of liver metastases in patients with colorectal carcinoma, 5-year survival rates are achieved in 25-38%, and two-thirds of patients will experience recurrent metastases. We examined percutaneous, minimally invasive, laser-induced thermotherapy (LITT) as an alternative outpatient procedure. Local tumor control rate and survival data were analyzed prospectively. METHODS: Between June 1993 and August 2000, 7148 laser applications were performed in 1981 lesions in 705 consecutive patients and 1653 treatment sessions. The complications of the procedure were evaluated by clinical examination and magnetic resonance imaging (MRI) and computed tomography. Local tumor control was evaluated by plain and contrast-enhanced follow-up MRI using T1- and T2-weighted spin-echo and gradient-echo sequences every 3 months after treatment. Cumulative survival times were calculated using the Kaplan-Meier method. RESULTS: The overall rate of complications and side effects was 7.5%. The rate of clinically relevant complications was 1.3%. Local tumor control rate after 3 months was 99.3%; 6 months after laser treatment, plain and contrast-enhanced MRI documented a local tumor control rate of 97.9%. In patients treated with MR-guided LITT for unresectable colorectal liver metastases, the mean survival was 41.8 months (95% confidence interval = 37.3-46.4 months). The 1-year survival rate was 93%, the 2-year survival rate was 74%, the 3-year survival rate was 50%, and the 5-year survival was 30%. In patients treated with LITT for liver metastases from breast cancer, the mean survival was 4.3 years (95% confidence interval = 3.6-5.0 years). CONCLUSION: In patients with liver metastases, local tumor destruction using minimally invasive, percutaneous LITT under local anesthesia results in improved clinical outcomes and survival rates and can be a potential alternative to surgical resection.

Laser-induced thermotherapy of malignant liver tumors: general principals, equipment(s), procedure(s)--side effects, complications and results.

PURPOSE: To prospectively evaluate the therapeutic potential of MR-guided and ultrasound-guided laser-induced thermotherapy (LITT) in patients with liver metastases and oligonodular hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Between June 1993 and June 2000 a total of 1608 LITT sessions was performed to treat 1914 lesions in 676 consecutive patients. The Nd-YAG laser fiber was introduced with a percutaneously positioned cooled application set. Qualitative and quantitative ultrasound and magnetic resonance (MR) parameters, as well as clinical data were evaluated. RESULTS: All patients tolerated the procedure well under local anesthesia; no relevant clinical complications were observed. The mean laser power was 25 W and the mean duration was 25 min. MR proved to be superior over computed tomography and ultrasound due the thermosensitivity of the MR sequences allowing a better visualization of the volume of laser-induced changes and their relation to the neighboring geographical structures. The ultrasound-guided LITT should be restricted for patients with contraindications for MR imaging monitoring and for selected patients with low diameter oligonodular HCC. In 95% of cases, we achieved a complete necrosis of the tumor and a 5-mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival in this group was 35 months (calculated with the Kaplan-Meier method). CONCLUSION: MR-guided, or ultrasound-guided, LITT appears to be a safe and effective treatment protocol for liver metastases and oligonodular HCC.

[Thermal ablation of liver metastases. Current status and prospects]. / Thermische Ablation von Lebermetastasen. Aktueller Stand und Perspektiven.

PURPOSE: To present thermal ablation of liver metastases via laser induced thermotherapy. MATERIAL AND METHODS: Different technical procedures of thermal ablation and online monitoring are used, as there are the MR-guided laser induced thermotherapy (LITT) and the radiofrequency ablation thermotherapy (RF). RESULTS: In a prospective non randomized study 606 patients with liver metastases were treated via MR-guided laser induced thermotherapy. Inclusion criteria were the exclusion of extrahepatic tumor spread and a number of metastases lower than 5 and a size lower than 50 mm in diameter. The local tumor control rate in the 3 month and 6 month control study was 98.3%, the complication rate 3.5% (clinically relevant: 1.2%). The mean survival rate was 40.9 months for all patients with liver metastases without statistically relevant differences for various primaries, like colorectal carcinoma, breast cancer and various other tumors. Results for radiofrequency are so far limited with incidence of a higher local tumor recurrence rate versus LITT. CONCLUSION: MR-guided LITT results in a high local tumor control rate with improved survival.

[Modern alternatives to resection of metastases--MR-guided laser-induced thermotherapy (LITT) and other local ablative techniques]. / Moderne Alternativen zur Metastasenresektion--MR-gesteuerte Laser-induzierte Thermotherapie (LITT) und andere lokal ablative Verfahren.

In patients with liver metastases of different primaries modern local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation (RF) are minimal invasive therapy options, if the patients were no candidates for liver surgery. A maximum of 5 cm lesion diameter and not more than 5 metastases without extrahepatic are treatable. MR-guided LITT is currently performed by means of implantable percutaneous catheter systems in local anesthesia and with outpatient management. RF is performed sometimes in general anesthesia and a hospital admission for some days. Liquid irrigated application systems are available both for LITT and for radiofrequency therapy and realized necrosis diameter up to 6 cm. At present LITT enables a local tumor control better than 98% for localized liver metastases without extrahepatic spreading patterns. In a group of 846 patients the average survival times were 4.0 years for patients with liver metastasis from different primary tumors. The data for RF ablation confirm the high value for tumor control for hepatocellular carcinomas with poorer results for liver metastases. Percutaneous MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number with an improvement of survival times.

Development of an ultrasensitive in vitro assay to monitor growth of primary cell cultures with reduced mitotic activity.

Primary cell cultures, such as isolated epithelial cells, neuronal cells, or hepatocytes are characterized by a very low mitotic activity. Monitoring of small changes in cell numbers requires staining with a DNA-specific dye with an extremely high sensitivity and a low inter- and intraassay variability. For this purpose, an ultrasensitive in vitro assay has been developed based on the fluorescent nucleic acid stain PicoGreen. PicoGreen has been shown to detect as little as 0.5 ng pure DNA or 10(2) cells (interassay SD < 10%, intraassay SD < 5%). This is far above the limit of sensitivity of conventional fluorochromes, such as Hoechst 33342 or propidium iodide. To obtain optimum efficacy of PicoGreen, cells were digested with papain for 20 h at 60 degrees C prior to staining. Under these conditions, the slope factor was calculated to be 0.105 relative fluorescence units (RFU)/cell, which is far superior to the slope factor of Hoechst 33342 (0.0137 RFU/cell) or propidium iodide (0.0077 RFU/cell). Analysis of the blank values revealed a very low autofluorescence of PicoGreen, which is only 1/50th of the autofluorescence of Hoechst 33342 and 1/5th of the autofluorescence of propidium iodide. Additional coating of the culture plates with extracellular matrix proteins to prevent cellular dedifferentiation did not influence the high sensitivity of PicoGreen. In conclusion, the PicoGreen-assay seems to be the method of choice when the growth capacity of primary cell cultures needs to be analyzed with high accuracy.

Dedifferentiation of human hepatocytes by extracellular matrix proteins in vitro: quantitative and qualitative investigation of cytokeratin 7, 8, 18, 19 and vimentin filaments.

BACKGROUND/AIMS: Liver cirrhosis and carcinogenesis are accompanied by an alteration in extracellular matrix material. Histological studies reveal upregulation of the intermediate filaments cytokeratins 8 and 18 and de novo synthesis of vimentin, and cytokeratin 7 or 19 in hepatocytes. The aim of this study was to investigate how these two processes are linked. METHODS: Human hepatocytes were seeded: (i) on the matrix components collagen I, IV, laminin, or fibronectin; (ii) on stoichiometrically different complete matrices, derived from human placenta (matrix I) or the Englebreth-Holm-Swarm tumor (matrix II), and (iii) inside a three-dimensional collagen I sandwich. Filament expression and assembly were measured by cytofluor analysis or confocal laserscan microscopy. RESULTS: The matrix components or complete matrices triggered enhancement of cytokeratins 8 and 18 and de novo synthesis of cytokeratins 7, 19 and vimentin in a characteristic way. Confocal images demonstrated a dense and uniform network of cytokeratin 18 in freshly isolated cells, which was "replaced" by a few, thick protein bundles within 20 days. Interestingly, newly synthesized cytokeratin 19 structurally resembled the cytokeratin 19 organization in biliary epithelial cells. Marked cytokeratin alterations could be partially prevented when hepatocytes were grown in a three-dimensional collagen sandwich. CONCLUSIONS: Pathological alterations to the chemical composition, molecular structure, or spatial arrangement of the liver matrix lead to specific changes in the intermediate filament pattern in human hepatocytes. We assume that degradation of the matrix results in pathological alterations to the hepatocyte-receptor matrix-ligand ratio, followed by a switch from physiological to pathological cell-activation.