Local Tumor Therapy Research Articles

Chromoendoscopy and intravital staining techniques

Chromoendoscopy and intravital staining techniques are synonymous methods for the endoscopic early detection of malignant changes in the intestinal tract. Endoscopic intravital staining involves the use of absorptive stains (methylene blue and Lugol’s solution), contrast stains (indigo carmine) and reactive stains (Congo red). Lugol’s iodine solution is used to identify superficial carcinomas in the squamous epithelium of the oesophagus. Methylene blue stains the specialized intestinal epithelium in Barrett’s oesophagus and, in addition to this, is helpful in the diagnosis of dysplasia.Intravital staining with indigo carmine contributes to contrasting and accentuating changed mucosal processes. Together with Cresyl violet, contrast staining is particularly important in detecting small, early malignant changes in the colon. The use of chromoendoscopy enables a biopsy diagnosis of superficial dysplastic changes and an accurate delineation of carcinomatous areas. In conjunction with the modern video-endoscopy (high-resolution endoscopy and magnification endoscopy), vital staining forms the diagnostic foundation for the detection of early malignant changes in the gastrointestinal tract. These techniques are therefore prerequisites to local endoscopic tumour therapy (mucosectomy). Despite their increasing acceptance, these methods must prove their diagnostic merit in randomized studies.

Tomographic Microtherapy

Minimally invasive techniques using endoscopes for image-guided therapy are now common in the field of surgery. Fast real-time radiologie imaging should be integrated into the procedure for increased safety in access and guidance techniques for endoscopes and instruments. The transparency of computed tomography (CT) guidance, magnetic resonance imaging, and electron beam tomography scan techniques allows precise guidance of instruments and endoscopes while permitting their diameter to be minimized. This guarantees safe and transparent access into the body, especially in high-risk areas such as the spine and brain. Combining both technologies has the potential to reduce complications and offers significant advantages in microinvasive operative procedures such as biopsies; local tumor therapy with lasers, radio frequency, or drugs; and percutaneous diskectomies or implants. CT is the golden standard for microtherapeutic procedures because of its precise tip discrimination.

Tomographic microtherapy.

Minimally invasive techniques using endoscopes for image-guided therapy are now common in the field of surgery. Fast real-time radiologic imaging should be integrated into the procedure for increased safety in access and guidance techniques for endoscopes and instruments. The transparency of computed tomography (CT) guidance, magnetic resonance imaging, and electron beam tomography scan techniques allows precise guidance of instruments and endoscopes while permitting their diameter to be minimized. This guarantees safe and transparent access into the body, especially in high-risk areas such as the spine and brain. Combining both technologies has the potential to reduce complications and offers significant advantages in microinvasive operative procedures such as biopsies; local tumor therapy with lasers, radio frequency, or drugs; and percutaneous diskectomies or implants. CT is the golden standard for microtherapeutic procedures because of its precise tip discrimination.

Radiofrequency ablation of the liver in vitro: increasing the efficacy by perfusion probes

Percutaneous radiofrequency interstitial thermal ablation is a new method in local tumour therapy. The aim of this study was to define the relations between the variable parameters and local efficacy in vitro and to evaluate optimal parameter combinations for this system. Furthermore, we studied the feasibility of increasing the volume of destroyed tissue using perfusion electrodes. Thermal lesions were produced with radiofrequency in ex vivo pig livers. In separate experiments the parameters wattage (5-30 watts), exposure time (1-15 minutes) and tip exposure were varied. The resulting areas of tissue necrosis coagulation were measured; in 30 of 90 cases the macroscopic findings were compared to the histological findings. Lesion size correlated with tip exposure, wattage and procedure duration up to 10 minutes. For a tip exposure of 2 cm (3 cm) the maximal lesion volume was 18.8 cm3 (33.2 cm3) at a wattage of 20 watts (30 watts) and a procedure duration of 10 minutes. The maximal cross- (length-) diameter of these lesions was 3 cm (4 cm) for 2 cm tip exposure and 3.6 cm (4.9 cm) for 3 cm tip exposure. The parameters wattage, procedure duration and tip exposure affect the size of lesions created with radiofrequency under ex vivo conditions. Perfusion electrodes make it possible to produce larger lesions than described for non-perfused electrodes. The ablation of hepatic neoplasms up to a size of 3 cm seems to be possible with a single electrode.

A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice.

Evaluation of potential new treatment strategies requires adequate experimental tumor models which resemble the clinical situation as closely as possible. The purpose of the present study was to establish a new human osteosarcoma spontaneous metastasis model using orthotopic transplantation of histologically intact tumor tissue into the tibia of nude mice. Intact tumor pieces, obtained from the 32nd serial passage of subcutaneously growing human osteosarcoma xenografts, were implanted into the proximal tibia in 31 nude mice. Animals were sacrificed and autopsied 2, 4, 6, and 8 weeks after transplantation and examined macroscopically and microscopically for local tumor growth and metastases. All mice developed local intratibial bone tumors that were radiographically and histologically similar to primary human osteosarcoma. Lung metastases were observed in all mice, local and distant lymph node metastases in 15 (48%), and liver metastases in 6 (19%) mice. The microscopic appearance of the metastases was similar to that observed in the donor patient's tumor, corresponding subcutaneous xenografts and orthotopically transplanted intratibial tumors. This spontaneous metastasis model of human osteosarcoma in nude mice may resemble a clinical situation and could thus be useful for studies on local tumor growth, metastasis formation and therapy.

Optimal regimes for local IL-2 tumour therapy

In this report we present studies on optimal regimes for regional IL-2 therapy, focused on dose, schedule and site of injection. Original data obtained in 2 murine tumour models show that all 3 factors are of importance. Anti-tumour responses were most effective when IL-2 was administered regionally 5 to 10 times, at doses ranging from 7,000 to 33,000 IU/day every day or every other day. This resulted in cure rates of more than 40% in mice bearing ascitic tumour that had also disseminated to liver and lungs. The importance of these data is discussed in the light of previous results of our group. These results illustrate that the doses and schedules used in this study are not effective exclusively in these 2 tumour models but may have a more general applicability.

Experimental local therapy of human melanoma with lytic magainin peptides

Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.

Intraoperative radiation therapy for pancreatic carcinoma. The choice of treatment modality.

Ninety patients with carcinoma of the pancreas treated between 1976 and 1990 were reviewed retrospectively. Intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) for localized but unresectable tumors (n = 29) prolonged survival significantly more than IORT alone (n = 16) (p < 0.01); it seems EBRT enhanced or contributed to the better results obtained with IORT plus EBRT. Moreover, IORT, alone or in combination, relieved pain. Adjuvant IORT for residual tumors (n = 20) might not effectively prolong survival, because the difference in survival rate between noncurative resection plus IORT and nonresection plus IORT in combination with EBRT was not significant. Curative tumor resection of stage III disease in combination with IORT (n = 9) resulted in significantly longer survival as compared with curative tumor resection alone (n = 8) (p < 0.05). It may be advisable to administer IORT in combination with EBRT to patients with advanced pancreatic carcinoma, avoiding aggressive tumor resection, when curative tumor resection cannot be performed.

Damage to Multicellular Human H-2 Glioma Spheroids Incubated With LAK Cells: An Ultrastructural Study

Local brain tumor therapy using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) has not proved to be effective in preliminary clinical trials. One obstacle to effective use of this therapy is ignorance about the events that follow contact of the LAK cells with glioma tissue. We used multicellular spheroids grown from human glioma cell lines as targets to study, in vitro, the effect of LAK cells against three-dimensional glioma tissue. Here we describe the ultrastructural changes in spheroids of H-2 glioma cells incubated in pellets of LAK cells for up to 24 hours. In H-2 spheroids, cellular damage was not restricted to the effector cell-target cell (effector-target) contact; it extended farther, at least partly because of nonspecific changes in the spheroid micromilieu. Formation of cytoplasmic blebs, a characteristic effect of T cells, natural killer cells, and LAK cells on single target cells, also occurs in H-2 spheroids, and it is not limited to the effector-target contact area either. These findings suggest that LAK cells release membrane-damaging agents that remain active outside the effector-target area, in the micromilieu of H-2 spheroid tissue.