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Biomedical subjects

B Scholl

Publications and source records attributed to B Scholl.

11 recordsLinked to original sources

Esophageal cancer as second primary tumor after breast cancer radiotherapy.

BACKGROUND: An increased risk of esophageal cancer has been reported in survivors of breast cancer treated with radiotherapy. This study further characterizes this association. METHODS: Through hospital databases, 118 patients (109 men, 9 women) treated for esophageal cancer between 1985 and 1993 were identified, of whom 37 had 60 synchronous or metachronous cancers. 5 women had primary esophageal cancer after having breast cancer, and are the subjects of this case-control study. RESULTS: All 5 women had been treated with radical mastectomy and adjuvant radiotherapy; none received chemotherapy. Their ages at the time of breast cancer ranged from 36 to 82 years; at esophageal cancer, 61 to 95 years. Time between radiotherapy and esophageal cancer varied from 13 to 31 years. All esophageal cancers were squamous cell carcinomas. Mean survival after esophageal cancer was 14.2 months. CONCLUSIONS: Radio-induced esophageal cancer can occur as a second primary cancer in women who survive at least 1 decade after mastectomy and adjuvant radiotherapy.

Adult↗

Angiogenesis of liver metastases: role of sinusoidal endothelial cells.

PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from pre-existing blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells are involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in BD IX rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal antibody. RESULTS: In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histological differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 microm, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.

Animals↗

Growth inhibition of liver metastases by the anti-angiogenic drug TNP-470.

OBJECTIVE: This study was undertaken in order to assess the efficacy of a potent angiogenesis inhibitor, TNP-470, on tumor growth in a syngeneic rodent model of liver metastases from colorectal cancer. BACKGROUND: New blood vessel formation is a prerequisite for primary and metastatic tumor growth. TNP-470, a synthetic derivative of fumagillin when subcutaneously transplanted into nude mice, inhibits endothelial cell proliferation and migration, as well as the growth of various human cancers. However, the antitumor effect of this drug has not been studied in models reproducing a natural metastatic environment. Since the liver provides an extensive vascular bed for secondary tumor growth, an anti-angiogenic strategy may therefore be less efficient for treating hepatic metastases than primary tumors. METHODS: 10(7) DHD K12 colon carcinoma cells were injected intrasplenically into syngeneic BD IX rats to produce diffuse liver metastases. TNP-470 (30 mg/kg/day) was administered on alternate days starting 4 days after tumor implantation. The animals were sacrificed after 4 weeks and their livers were processed for histologic examination. In both the treatment and control groups (n=7), tumor volume was determined using a computerized analytical system, and tumor microvessel density was measured by immunostaining with anti-von Willebrand Factor monoclonal antibody. RESULTS: In vitro, TNP-470 demonstrated a direct toxicity towards the DHD K12 cell line with an IC50 of 0.1 microg/ml. Metastases were present in all animals from both groups. Liver weight (15.2 g vs 11.7 g, p=0.01), and tumor volume (1218 mm3 vs 406 mm3, p=0.03) were significantly reduced in the TNP-470 group compared to the control group. Tumor microvessel density was not statistically different between the two groups (67 vs 63 microvessels/x200 field, p=0.41). CONCLUSION: TNP-470 inhibits the growth of liver metastases in a syngeneic rat model of colorectal cancer. The mechanism responsible for this effect remains unclear, but may involve a combination of anti-angiogenic and direct cytotoxic effects.

Angiogenesis Inhibitors↗

Permanent access to the portal vein in rats: an experimental model.

A safe and reproducible method for placement of indwelling catheters into the portal venous system is a prerequisite for improved delivery of anticancer drugs to experimental liver metastases. Due to the lack of tumor models in large animals and the difficulty in establishing permanent access to the portal vein in rodents, this type of model has rarely been described in the laboratory setting. We propose a simple, minimally invasive method for repeated portal vein injections in rats. A vascular access device was used, which remained patent for periods of up to 3 months. Placement and support of the catheter tip in the portal vein was performed with a technique designed to avoid portal thrombosis and infections. Permanent portal vein access in a rodent model of liver metastases will be invaluable for the development of novel therapeutic strategies.

Animals↗

Value of laparoscopic staging for Hodgkin disease.

Because of the potential for complications with laparotomy and splenectomy, and the widespread use of combination chemotherapy as first-line treatment, surgical staging is now performed in only 30% of patients with Hodgkin disease. Laparoscopic staging has rarely been reported. Three patients with the nodular sclerosis cell type of Hodgkin disease underwent laparoscopic staging. Mean operative time was 207 minutes. No conversion to laparotomy was necessary. There were no peri- or postoperative complications and no deaths. Mean blood loss was negligible. The pathologist deemed all liver and lymph nodes biopsies adequate for histologic analysis. Stage IA and IIA were confirmed in two patients: one patient with stage IIA was upstaged to IIIA after surgery. Performed by an experienced team, laparoscopy is the procedure of choice for abdominal staging of patients with Hodgkin disease.

Adult↗

[Cecum volvulus].

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Abdomen, Acute↗

What's next for managed care? Panel discussion.

Change continues to be health care's only constant in the United States. As enrollment in managed care organizations skyrockets, the glare of public scrutiny intensifies. Success is no longer as simple as undercutting traditional fee-for-service providers; MCOs have to become more responsive to consumer needs as they compete with one another. Whether substantial set of values or mere buzzword, quality is the lingua franca of the MCO arena. Although MCO executives attribute the concept's ubiquity to many factors, the common denominator is staying competitive in a high-growth industry. Along with the elimination of the gatekeeper, a major trend to watch for is the rise of industry oversight provided by standardized practice guidelines. MCO executives recognized that implementing such measures will streamline operations and make MCOs more user-friendly.

Efficiency, Organizational↗

Adenovirus-mediated gene transfer into selected liver segments using a vascular exclusion technique.

Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.

Adenoviridae↗