Laparoscopic liver resection: experience of 53 procedures at a single center

Background/Purpose The short-term outcome following laparoscopic liver resection at a single center is presented.Methods Fifty-three procedures were carried out in 47 patients, between August 1998 and April 2004 (6 patients were resected on two occasions). A previous laparotomy and/or hepatectomy had been done in 83% and 26% of the procedures, respectively. Colorectal metastasis was the main indication for treatment (42/53). A total laparoscopic approach was applied.Results Three of the 53 (6%) procedures were converted to laparotomy. In one additional procedure, radiofrequency ablation was done instead of resection. Sixty liver resections were done during the 49 procedures completed laparoscopically as planned (9 patients had concomitant resections performed). Nonanatomic (45/60) and anatomic (15/60; left lobectomies) resections were done. Tumor tissue was found in the resection margins of 6% of the specimens. The free margin was very short in 8% of the specimens. The morbidity was 16%. There was no mortality. Blood transfusions were given following 26% of the procedures. The median hospital stay was 3.5 days (range, 1–14 days) and the median number of days on which there was a need for opioids was 1 (range, 0–11 days).Conclusions Laparoscopic liver resection can be performed safely and seems to offer short-term benefits to the patients. Randomized studies are required to further evaluate the potential benefits of this treatment.     

Research in a dental practice setting

There is a shortage of research from dental practice. The aim of this article is to stimulate more interest in dental research. This is done by explaining the basic principles of doing research in a dental practice setting. Examples are taken from the author's own practice. Emphasis is placed on the following points: how to develop and research ideas; factors specific to dental practice; how articles and journals are rated; making a protocol for the study; examiners' reliability and statistical analysis.     

Immunotoxin treatment targeted to the high-molecular-weight melanoma-associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme

OBJECT: The aim of this study was to target immunotoxin treatment to the high-molecular-weight melanoma-associated antigen (HMW-MAA) and thereby examine any changes in the survival of immunodeficient rats with human glioblastoma multiforme (GBM). METHODS: To target treatment specifically to human glioma cells, Pseudomonas exotoxin A (PE) was conjugated to the 9.2.27 antibody, which recognizes the HMW-MAA. Treatment of the antigen-positive glioma cell line U87MG with the resulting 9.2.27-PE caused cytotoxicity with a median inhibitory concentration of 1 ng/ml. Intratumoral 9.2.27-PE treatment of intracranial U87MG tumors in nude rats prolonged the survival of these animals by 43% compared with controls. In additional studies on the use of this targeted treatment, the authors precultured freshly dissected glioblastoma multiforme (GBM) biopsy tissue for 1 to 2 weeks. Inoculation of this tissue into the rat brain resulted in diffuse infiltrative gliomas. The markers glial fibrillary acidic protein and S100 protein were found to be expressed in the original biopsy specimens, as well as in the glioma xenografts in nude rat brains. Intratumoral immunotoxin treatment of such established tumors with 9.2.27-PE was effective and prolonged survival time from 30% to as high as 90% in animals with tumors originating from four different GBM specimens. CONCLUSIONS: Targeted treatment of highly invasive GBMs proved effective, and these results emphasize the clinical relevance of this antigen as a target molecule for immunotoxin treatment of human GBMs.     

Intestinal injury after thoracic aortic cross-clamping in the pig

BACKGROUND: The mucosal surface epithelium is an essential part of the functional intestinal barrier, but its structural response to ischemia/reperfusion is only partly characterized. The purpose of this study was to provide a detailed morphological evaluation of intestinal surface epithelium after aortic cross-clamping. MATERIAL AND METHODS: Pigs were subjected to thoracic aortic cross-clamping for 60 min and subsequent reperfusion for 120 min. Tissue blood flow and high-energy phosphates were measured with microspheres and HPLC, respectively. Urinary excretion of (14)C polyethylene glycol (MW 4000 Da) (PEG-4000), loaded into an intestinal loop, provided an index of intestinal permeability. RESULTS: Jejunal blood flow was restored at 10 min after aortic declamping. Denudation of the basement membrane of the intestinal villi tips, as a consequence of epithelial shedding, increased markedly during the initial 60 min of reperfusion (P = 0.002). During the following 45 min, the denuded basement membrane was partly covered with low cuboidal and squamous-shaped cells extending lamellipodia over a wavy basement membrane. Restoration of ATP at 60 min after aortic declamping correlated inversely to the extent of denuded basement membrane (r = 0.75, P = 0.032). Permeability of PEG-4000 increased markedly after aortic declamping and was linearly correlated to the area of denuded basement membrane (r = 0.87, P = 0.01). CONCLUSIONS: Reperfusion for 2 h after aortic cross-clamping is associated with initial aggravation of ischemia-induced injury in the porcine jejunum, but thereafter with restitution of the surface epithelium. Restoration of ATP may be important to avoid intestinal injury after ischemia. Increased permeability of a macromolecule in response to reperfusion is closely correlated to injury of the surface epithelium.     

Early detection of regional myocardial ischemia in ex vivo piglet hearts: MR imaging with magnetization transfer

The effects of regional myocardial ischemia and reperfusion on magnetization transfer (MT) contrast were investigated in an ex vivo perfused piglet heart model. The extent of the ischemic area was defined with perfusion magnetic resonance (MR) studies performed with use of extracellular contrast agents. Relative MT contrast was calculated for a total of 106 regions of interest in nine hearts. In the areas defined as being severely ischemic in the perfusion studies, a small but significant increase in the MT contrast of 18% ± 9 (standard deviation) (n = 35) was found as early as 10 minutes after the start of ischemia. This contrast difference was reduced to 11% ± 10 after 2 hours of total occlusion. The contrast between normal and ischemic tissue can be explained in part by the effect of inflowing blood, which leads to changes in both equilibrium magnetization and the apparent T1 of the perfused tissue. However, theoretical estimation suggests that these flow-related changes would produce a maximal relative change in MT contrast of approximately 4%. The most likely explanation for the rest of the observed changes is alteration in the distribution of cellular water related to the so-called intracellular edema that is known to be associated with the acute phase of myocardial ischemia.     

Primary gene‐engineered neural stem/progenitor cells demonstrate tumor‐selective migration and antitumor effects in glioma

The prognosis of patients with glioblastoma multiforme (GBM) is generally poor after surgical tumor resection. With the aim of developing new adjuvant therapeutic strategies, we have investigated primary neural stem/progenitor cells (NSPC) in co‐cultures with glioma cells, and in a model of gene therapy on aggressively growing malignant glioma. NSPC exhibited tropism towards medium conditioned by glioma cells, and in adherent low‐cell density co‐culture, were attracted to, and fused with, tumor cells. Similarly, within 24–48 hr of co‐culture in suspension, NSPC‐tumor hybrids were observed, representing 2–3% of the total cell population. NSPC were then coinjected into mouse brain with GBM cells, employing NSPC expressing cyclophosphamide (CPA)‐activating enzyme cytochrome p450 2B6 (CYP2B6), which catalyzes CPA prodrug transformation into membrane diffusible DNA‐alkylating metabolites. Upon CPA administration, NSPC containing CYP2B6 elicited substantial impairment of tumor growth. When implanted intracerebrally at a distant site from the tumor, gene‐engineered NSPC specifically targeted GBM grafts, after traveling through brain parenchyma, and hindered tumor growth through local activation of CPA. Directed migration of primary NSPC corresponded closely with intracerebral and tumoral pattern of expression of vascular endothelial growth factor, which is a motility factor for NSPC. Overall, these findings indicate that therapeutic gene delivery mediated by primary NSPC is a potentially valid strategy for treatment of high‐grade gliomas.     

In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: a study of liver and muscle disposition of fleroxacin in humans

Magnetic resonance spectroscopy of fluorine (19F) has been used to noninvasively study the in vivo pharmacokinetics of a model drug, fleroxacin (a fluoroquinolone antibiotic agent), in healthy human subjects. After oral administration, fleroxacin was detected in 19F magnetic resonance spectra from both liver and calf muscle and four magnetic resonance examinations were undertaken during a 24-hour period. By combining plasma analysis by high performance liquid chromatography with the magnetic resonance data, the following pharmacokinetic parameters (mean values) were obtained: tmax, 1.4, 4.6, and 5.6 hours in liver, plasma, and muscle, respectively; Cmax, 53, about 250, and about 60 mumol/L in plasma, liver, and muscle, respectively; t1/2, 4.4 hours (fast phase) and 10.8 hours (slow phase) in liver and 14.2 hours in plasma. The study documents for the first time the potential use of 19F magnetic resonance spectroscopy to noninvasively observe the time-related changes of a fluorine-containing drug in human tissues after oral administration.