Faculty Bibliography

PURPOSE: Concern is frequently raised regarding the tolerance of irradiation over a joint space. The purpose of this study was to determine the outcome in terms of relapse and potential complications in patients with knee and elbow soft tissue sarcoma treated with limb-sparing surgery with or without adjuvant radiotherapy (RT). METHODS AND MATERIALS: A review of our prospective database between June 1982 and December 1999 identified 86 adult patients with primary soft tissue sarcoma arising from the knee (n = 65; 76%) or elbow (n = 21; 24%) treated with limb-sparing surgery. Tumors had high-grade histologic features in 72% and were >5 cm in 48% of patients. Adjuvant RT was given to 46 (54%) of 86 patients. The type of RT was postoperative external beam RT in 63% and brachytherapy in 37%. Of the 46 patients who received RT, 85% (n = 39) had deep, 78% (n = 36) high-grade, and 54% (n = 25) >5-cm tumors. Complications were assessed in terms of wound complications requiring repeated surgery, bone fracture, nerve damage, and joint stiffness. RESULTS: With a median follow-up of 48 months (range 4-175), the 5-year actuarial rate of local control, distant control, and overall survival was 75% (95% confidence interval [CI] 64-85%), 82% (95% CI 73-91%), and 81% (95% CI 71-91%), respectively. The 5-year local control rate for patients who received RT was 80% vs. 71% for those who did not (p = 0.3). The type of RT did not significantly influence the local control rate. Patients treated with external beam RT had a 5-year local control rate of 84% compared with 73% for those treated with brachytherapy (p = 0.4). On multivariate analysis, tumor size >5 cm retained its significance as an independent predictor of poor local control (p = 0.04; relative risk 3; 95% CI 1-6). In addition, high-grade histologic features emerged as an independent predictor of local recurrence (p = 0.02; relative risk 4; 95% CI 1-20). No statistically significant difference was found between the RT and no-RT group in terms of the 5-year actuarial rate of wound reoperation (10% vs. 3%, p = 0.1), bone fracture (3% vs. 5%, p = 0.5), or nerve damage (6% vs. 3%, p = 0.5). Joint stiffness was significantly higher in the RT group (24% vs. 0%, p = 0.001), but this stiffness was severe to moderate in only 2 patients. CONCLUSION: On the basis of the findings of this retrospective review, adjuvant RT seems to be relatively well tolerated despite the inclusion of part of the joint space in the irradiation portal. Joint stiffness was seen more frequently with adjuvant RT, but it was moderate to severe in only a small number of patients.

The authors present the case of a patient who suffered from progressive cranial nerve dysfunction, radiographically documented brainstem compression, and peduncular hallucinosis after undergoing endosaccular coil placement in a giant basilar apex aneurysm. Symptom resolution was achieved following clip ligation of the basilar artery. The pathogenesis of aneurysm mass effect due to coil placement is discussed and the pertinent literature is reviewed

Conjoined twins occur in approximately one of every 50,000 to 200,000 births. Atypical or parasitic conjoined twins result from the embryonic death of one twin, which leaves behind body parts vascularized by the primary twin. Omphalopagus refers to conjoined twins joined at the level of the umbilicus. The authors report a case of atypical omphalopagus involving an acardiac, acephalic, parasitic twin and a host twin with a large omphalocele, transposition of the great arteries, and aortic coarctation. The authors briefly review reported cases of parasitic omphalopagus and emphasize the role of intensive neonatal care, preoperative planning, and staged surgical intervention in the successful management of complicated variants.

BACKGROUND: This paper examines the mechanism of ultrasonic enhanced drug delivery from Pluronic micelles. In previous publications by our group, fluorescently labeled Pluronic was shown to penetrate HL-60 cells with and without the action of ultrasound, while drug uptake was increased with the application of ultrasound. METHODS: In this study, the amount of uptake of two fluorescent probes, Lysosensor Green (a pH-sensitive probe) and Cell Tracker Orange CMTMR (a pH-independent probe), was measured in HL-60 and HeLa cells. RESULTS: The results of our experiments show that the increase in drug accumulation in the cells as a result of ultrasonication is not due to an increase in endocytosis due to ultrasonication. CONCLUSIONS: We hypothesize that sonoporation plays an important role in the acoustically activated drug delivery of chemotherapy drugs delivered from Pluronic micelles.

We investigated the effect of chronic administration of morphine on noxious stimulus-induced antinociception (NSIA) produced by intraplantar capsaicin injection. In the untreated (naive) rat, we previously found that NSIA depends on activation of dopamine, nicotinic acetylcholine, and mu- and delta-opioid receptors in nucleus accumbens. Rats chronically implanted with subcutaneous morphine pellets demonstrated tolerance to the antinociceptive effects of acute systemic morphine administration but did not show cross-tolerance to NSIA. Morphine pretreatment, however, significantly reduced NSIA dependence on intra-accumbens opioid receptors but not on dopamine or nicotinic acetylcholine receptors. As observed in naive rats, intra-accumbens microinjection of either the dopamine receptor antagonist flupentixol or the nicotinic receptor antagonist mecamylamine blocked NSIA in rats tolerant to the antinociceptive effects of morphine, but, in contrast to naive rats, intra-accumbens microinjection of either the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7 amide or the delta-receptor antagonist naltrindole failed to block NSIA. These findings suggest that although NSIA is dependent on nucleus accumbens opioid receptors in the naive state, this dependence disappears in rats tolerant to the antinociceptive effects of morphine, which may account for the lack of NSIA cross-tolerance. In separate experiments, intra-accumbens extracellular dopamine levels were measured using microdialysis. Dopamine levels increased after either capsaicin or systemic morphine administration in naive rats but only after capsaicin administration in morphine pretreated rats. Thus, intra-accumbens dopamine release paralleled antinociceptive responses in naive and morphine pretreated rats