Percutaneous isolated liver perfusion for treatment of hepatic malignancy: preliminary report.

Chemotherapy for primary or metastatic hepatic malignancy is limited by poor tumor response and dose-related systemic toxicity. As an alternative to chemotherapy infusion by vein or by the hepatic artery, the authors have developed a percutaneous technique of isolated liver perfusion that allows the regional delivery of high-dose chemotherapy to the liver with little systemic toxicity. After placement of a hepatic artery infusion catheter, an 18-F double-balloon catheter is placed into the inferior vena cava through the opposite femoral vein. Balloons are inflated above and below the hepatic veins, thus isolating hepatic venous outflow. The effluent passes through fenestrations in the catheter and is pumped through charcoal hemoperfusion filters where the drug is removed. The filtered blood is returned to the patient through the internal jugular vein. Fifteen treatments have been conducted in eight patients in a phase I dose-escalation study with use of 5-fluorouracil (5-FU). While it is premature to assess tumor response to isolated liver perfusion, the data demonstrate that the procedure is safe and is tolerated by patients. Pharmacokinetic studies show a 5-FU extraction of up to 85%, with minimal drug leakage into the systemic circulation. This technique shows potential for improving liver tumor response while decreasing systemic toxicity.     

117Care of the Thermally Injured Breast

Introduction : Thermal injury to the female breast is one of the most challenging aspects of aesthetic burn surgery today. As the ability to provide coverage for large body surface injuries has progressed greatly in recent years; attention can now be directed towards achieving aesthetically pleasing results. Breast reconstruction in the burn patient can be accomplished in several ways. In planning the reconstruction, one must account for gender, age, and stage of breast development at the time of injury. The following is the treatment protocol utilized at our institution. After determining the level of injury the injured area is cleansed and treated with topical anti‐microbial agents such as Silvadene. If the decision is made to excise and graft the injured area one of two algorithms is followed. The first choice involves excising the burn and placing a split thickness skin graft to the area involved. This is done by placing a sheet graft and using aerosolized fibrin sealant to affix it to the wound bed. If the burn involves deeper elements of tissue then a second approach is taken which includes excision of the burn down to the level of fascia with preservation of the breast mounds and the nipple areola complex (NAR). The (NAR) is spared excision and allowed to heal. Reconstruction of the (NAR) can be deferred for a secondary procedure depending upon the response to primary healing. A split thickness skin graft is then applied to the area of injury. Again a sheet graft is preferred and fibrin sealant is utilized to improve graft fixation and contour. We attribute our excellent results to the sheet grafts and fibrin sealant used. It should be noted that the increased vascularity of the breast fat when compared to fat located elsewhere in the body allows the grafts to adhere and survive on this generally difficult to graft surface. Methods : We identified five female patients at our institution over the last 18 months with thermal injuries to the breasts. Each patient was placed into one of the two treatment algorithms. Results : The five patients had excellent outcomes. Breast mounds and symmetry were preserved. Further development of the breast was allowed in each patient. One patient even underwent a breast augmentation after surviving a 50% TBSA injury. Proper use of fibrin sealant and sheet grafts account for the excellent results seen at this institution. Conclusion : Following careful evaluation of the burned female breast cosmetically and functionally acceptable results can be attained when following our institution’s protocol for breast reconstruction in the female burn victim.     

Right hemothorax: an unusual presentation of ruptured infrarenal abdominal aortic aneurysm

The authors describe what they believe is the first reported case of rupture of an infrarenal abdominal aortic aneurysm into the right pleural cavity. A 75-year-old woman presented simultaneously with two common causes of severe abdominal pain and hypotension: perforated duodenal ulcer and ruptured abdominal aortic aneurysm. The absence of an infrarenal retroperitoneal hematoma delayed the diagnosis of rupture of the abdominal aortic aneurysm and the terminal event was exsanguination into the right pleural cavity through an erosion in the right hemidiaphragm.     

Histopathologic and dietary prognostic factors for canine mammary carcinoma

Summary Histologic and dietary prognostic factors for survival following naturally occurring breast cancer were studied for 145 pet dogs. Information was collected from the dog's owner and veterinarian regarding medical and reproductive history, nutritional status, treatment, tumor recurrence, and length of survival. The usual intake of all dog and table foods consumed 1 year prior to diagnosis was obtained using a validated quantitative food frequency questionnaire. A histologic malignancy score was derived based on 7 histopathologic criteria. The mean age of the dogs was 10.4 ± 2.5 years; 37% had been ovariohysterectomized prior to diagnosis. Product-limit estimates of survival indicated that 6 factors, namely body conformation 1 year prior to diagnosis (p = 0.03), histologic tumor type (p = 0.004), histologic malignancy score (p = 0.02), histologic invasion (p = 0.002), tumor recurrence (p<0.0001), and completeness of surgery (p = 0.01) were of prognostic significance. In addition, when dogs were characterized by the percent of total calories they derived from fat and protein, the median survival time for dogs in the low fat group (<39%) with protein >27%, 23–27%, and <23% was 3 years, 1.2 years, and 6 months, respectively (p = 0.008). For dogs in the high fat group (39%), there was no difference in survival for the different intake levels of dietary protein (p = 0.84). When these data were fitted to a proportional hazards model, recurrence, histologic score, tumor type, percent of calories derived from protein, fat group, and a protein-fat group interaction term were statistically significant. Predicted 1 year survival for dogs on a low fat diet with 15%, 25%, and 35% of total calories derived from protein was 17%, 69%, and 93%, respectively.     

Sequence specificity of mutations induced by benzo[a]pyrene-7,8-diol-9,10-epoxide at endogenousaprt gene in CHO cells

We have determined the spectrum of mutations induced, by±trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene (BPDE) at the endogenous aprt locus in an hemizigous Chinese hamster ovary cell line exposed to 0.7 M BPDE. Southern analysis of 59 independent mutants revealed no major genomic alterations, indicating that gene inactivation was the result of a point mutation. This conclusion was confirmed by the cloning and sequencing of 21 of these mutants. The predominant mutation, the GCTTA transversion, comprised 62% of the spectrum, but other base pair substitutions and frameshifts were recovered. An examination of the target sequences for BPDE mutation revealed that mutations were localized within runs of GC base pairs. However, approximately half of these GC runs involved a particular sequence—a run of guanines flanked by adenine residues. Of seven such sites within the coding sequence ofaprt, mutations were clustered within five of them. This class of sequence occurs at codon 61 of the human C-Ha-ras1 protooncogene and may account for the selective activation of this codon by BPDE.     

Differential effects of short- and long-pulsewidth laser exposures on retinal ganglion cell response

Time-dependent effects of laser exposures on rhesus monkey retinal ganglion cells were studied with a Q-switched, doubled Nd:glass laser, which produced 20 nsec pulses of 530-nm light, and a continuous-wave (CW) argon laser (514.5 nm), which produced exposures of 0.1-msec to 0.1-sec duration. Ganglion cell activity was recorded in situ by means of an intraocular electrode. Ganglion cells exposed to a single 20-nsec exposure, at a sublesion intensity, produced a 60-90 sec discharge of action potentials and exhibited a 2 log or greater elevation of light threshold, depending on beam size and intensity. At equivalent energy levels, the longer exposures produced the same or slightly weaker effects. This result is not as straightforward as it seems. Submillisecond flashes bleach no more than 50% of the visual pigment because of photoregeneration. The Dowling-Rushton relation predicts that a 50% bleach should produce only a 1.5 log loss of cone sensitivity. Exposures longer than 1 msec should not photoregenerate pigment (ie, more pigment will be bleached for a given exposure intensity). In view of the probable differences in pigment bleaching, it appears that the Q-switched laser light adapts the cells out of proportion to the visual pigment actually bleached--a single-cell analogue of Rushton's "theta" effect.     

Androstenedione may organize or activate sex-reversed traits in female spotted hyenas.

Spotted hyenas (Crocuta crocuta Erxleben) present a unique syndrome of reversal in behavioral and anatomical distinction between the sexes: females are heavier and more aggressive than males and dominant over them. The female's external genitalia include a false scrotum and a fully erectile pseudopenis through which mating and birth take place. Results of studies of circulating testosterone levels in wild spotted hyenas do not account for the "male-like" characteristics of the female. Androstenedione, however, is consistently higher in females than in males, particularly during early infancy. Experiments on rodents show that androstenedione can be a potent organizer of anatomical and behavioral differentiation. This study suggests that it may also produce the profound virilization of female spotted hyenas.     

The relationship of drug program environmental variables to treatment outcome

The Moos Community Oriented Program Environment Scale (COPES) was administered to 244 adolescent clients and 131 drug counselors in 30 "drug-free" outpatient drug treatment programs. Four of the COPES factor scores were found to predict significantly to treatment outcome (as measured by reduction in drug use): client ratings of "Spontaneity", and staff ratings of "Personal Problem Orientation", "Practical Problem Orientation", and "Order and Organization". The more positive the ratings of the program environments, the greater the reduction in client-reported drug use from admission to discharge. The "discrepancies" (differences) between staff and client perceptions of the programs on two of the COPES factors ("Autonomy" and "Staff Control") were also found to predict significantly to treatment outcome (as measured by reduction in drug use). The greater the discrepancy, the less successful was the treatment outcome. In the programs in which the clients tended to perceive the staff as less encouraging of client autonomy and as exercising more control over the clients relative to the staff's perceptions of these relationships, the clients tended to have less successful treatment outcomes. One possible interpretation of this finding might be that in the programs which have client populations that are more poorly motivated and more resistant to treatment, the clients will not only tend to have poorer treatment outcomes but will also perceive the program environment more negatively and thus will tend to disagree more with the staff's perceptions of the program.