Rationale for clinical trials of coagulation: reactive drugs in hepatocellular carcinoma

Evidence for the regulation of cancer growth by components of the blood coagulation mechanism provides abundant opportunity for the development of novel hypotheses for the experimental treatment of malignancy. Information available on the heterogeneity in mechanisms of interaction between various cancer cell types, and procoagulant and fibrinolytic pathways, platelets, glycosaminoglycan-regulated growth factors and cell-adhesion molecules indicates that insightful clinical trial design may allow targeting of individual cancer cell types with agents capable of intercepting mechanisms of growth control that are relevant to specific tumor types. This paper reviews the evidence that the common anticoagulant, heparin, inhibits hepatocellular carcinoma cell proliferation and hepatocellular carcinoma tumor dissemination in experimental animals. Clinical trials of heparin performed to date have shown increased tumor response rates and survival in other tumor types. Expression of urokinase-type plasminogen activator by hepatocellular carcinoma cells enhances tumor cell proliferation, motility, invasiveness and metastatic dissemination. Inhibition of the urokinase-type plasminogen activator/plasmin system by protease inhibitors such as aprotinin (Trasylol, Bayer) have shown improvement in the clinical course of certain tumor types. These data suggest that drugs that are well-known in the field of vascular medicine may find a role in the treatment of hepatocellular carcinoma, a common tumor type that has resisted containment by other means.     

Proteomic profiling in microdissected hepatocellular carcinoma tissue using ProteinChip technology

At present, the molecular mechanisms of hepatocellular carcinogenesis are not well understood. It is known, however, that cancer development and progression are accompanied by profound changes at the cellular and subcellular level, involving RNA/DNA and protein structure and function. Therefore, high-throughput, proteomic techniques targeting these biological molecules may provide novel insights into HCC genesis and prognosis. We characterized tissue protein profiles from 10 HCC patients using ProteinChip technology (SELDI) which is able to detect minute amounts of proteins and moreover to analyze complex protein pattern. Therefore, after histopathological examination, proteins from kryostat sections of non-tumorous hepatic tissue as well as from central and peripheral tumor areas were isolated from complete histological sections or from selected and microdissected tissue areas. Analysis on the SAX and WCX ProteinChip Arrays revealed 14-26, and 25-29 differentially expressed peaks respectively, which characterized non-tumorous and tumor tissue (p< or =0.05). One feature which allows differentiation between central tumor and peripheral tumor regions could only be detected in microdissected tissue. Using ProteinChip technology in combination with tissue microdissection it is possible to investigate complex changes at the protein level in hepatocellular cancer associated with tumor development and progression.     

Endobronchial high-frequency jet ventilation for endobronchial laser surgery: an alternative approach

IMPLICATIONS: We describe a technique of one-lung high-frequency jet ventilation surgery with continuous monitoring of airway pressures that achieves satisfactory operating conditions with less complications than other similar approaches.     

A population-based study of inflicted traumatic brain injury in young children

Context  Physical abuse is a leading cause of serious head injury and death in children aged 2 years or younger. The incidence of inflicted traumatic brain injury (TBI) in US children is unknown. Objective  To determine the incidence of serious or fatal inflicted TBI in a defined US population of approximately 230 000 children aged 2 years or younger. Design, Setting, and Subjects  All North Carolina children aged 2 years or younger who were admitted to a pediatric intensive care unit or who died with a TBI in 2000 and 2001 were identified prospectively. Injuries were considered inflicted if accompanied by a confession or a medical and social service agency determination of abuse. Main Outcome Measure  Incidence of inflicted TBI. Multivariate logistic regression models were used to compare children with inflicted injuries with those with noninflicted injuries and with the general state population aged 2 years or younger. Results  A total of 152 cases of serious or fatal TBI were identified, with 80 (53%) incurring inflicted TBI. The incidence of inflicted traumatic brain injury in the first 2 years of life was 17.0 (95% confidence interval [CI], 13.3-20.7) per 100 000 person-years. Infants had a higher incidence than children in the second year of life (29.7 [95% CI, 22.9-36.7] vs 3.8 [95% CI, 1.3-6.4] per 100 000 person-years). Boys had a higher incidence than girls (21.0 [95% CI, 15.1-26.6] vs 13.0 [95% CI, 8.4-17.7] per 100 000 person-years). Relative to the general population, children who incurred an increased risk of inflicted injury were born to young mothers (21 years), non–European American, or products of multiple births. Conclusions  In this population of North Carolina children, the incidence of inflicted TBI varied by characteristics of the injured children and their mothers. These data may be helpful for informing preventive interventions.      

What is the best possible design of temporary anterior mandibular osteotomy? A histomorphological animal study.

When squamous cell carcinomas in the oral cavity have advanced to the size of T2 to T3 or when they start to encroach on the middle, occasionally it is necessary to divide the mandible at the parasymphysis and swing the hemimandible away from the midline for intraoral exposure of tumor resection. The osteotomy is usually performed in either a straight vertical cut, in a step-cut fashion, or in a dove-tail geometric configuration. The design of the geometric pattern of the osteotomy determines whether or not the postoperative period is prolonged. The authors analyzed the best possible design of temporary anterior mandibular osteotomy. In an animal study of 12 Goettingen minipigs (GMPs) the authors investigated the best possible design of geometric pattern of mandibular osteotomy and the fragment healing process. Their primary interest was directed at the histomorphological bone-healing process after straight vertical bone cut, step-cut fashion, and dove-tail osteotomy of the mandible, and rigid fixation with an osteosynthesis plate. From this study it can be concluded that the dove-tail osteotomy of the mandible is the best possible design of temporary anterior mandibular osteotomy in preventing pseudoarthrosis due to the mainly primary bone contact and gap healing process.     

Breast and axillary tissue MR imaging: correlation of signal intensities and relaxation times with pathologic findings

We tested a variety of inversion-recovery (IR) and spin-echo (SE) sequences by imaging the breast masses of 22 patients before surgery and 23 tissue specimens with magnetic resonance (MR) imaging at 0.6 T to determine the most effective pulse sequences to evaluate breast disease. An SE pulse sequence using a long repetition time (TR) of 1,600 msec and a long echo time (TE) of 90 msec was found to be the most sensitive in depicting carcinoma in the excised tissue specimens, with all of the carcinomas (n = 15) demonstrating irregular areas of higher signal intensity (SI) than that of the adjacent fat. However, only five of 11 breast carcinomas present in the preoperative patients produced a higher SI than that produced by fat on the same T2-weighted sequence. Five of the remaining six carcinomas in the preoperative patients appeared as localized distortions of fibroductular architecture on both T2-weighted SE and IR sequences. In axillary tissue specimens, both metastatic carcinoma and hyperplastic lymph nodes produced a high SI on T2-weighted SE sequences. However, metastatic carcinoma had a significantly longer T2 relaxation time than did hyperplastic lymph nodes.