Kenneth E. Marks

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

In this randomized, prospective, double-blinded clinical trial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the perioperative use of allogeneic blood transfusion. One-hundred-eighty-one elective surgical patients were enrolled at 19 clinical sites from 1996 to 1998. Selection criteria included anticipated transfusion of 2–4 blood units, aortic repair, and major joint or abdomino-pelvic surgery. Once a decision to transfuse had been made, patients received initially up to 3 250-mL infusions of 10% DCLHb (n = 92) or 3 U of packed red blood cells (PRBCs) (n = 89). DCLHb was infused during a 36-h perioperative window. On the day of surgery, 58 of 92 (64%; confidence interval [CI], 54%–74%) DCLHb-treated patients received no allogeneic PRBC transfusions. On Day 1, this number was 44 of 92 (48%; CI, 37%–58%) and decreased further until Day 7, when it was 21 of 92 (23%; CI, 15%–33%). During the 7-day period, 2 (1–4) units of PRBC per patient were used in the DCLHb group compared with 3 (2–4) units in the control patients (P = 0.002; medians and 25th and 75th percentiles). Mortality (4% and 3%, respectively) and incidence of suffering at least one serious adverse event (21% and 15%, respectively) were similar in DCLHb and PRBC groups. The incidence of jaundice, urinary side effects, and pancreatitis were more frequent in DCLHb patients. The study was terminated early because of safety concerns. Whereas the side-effect profile of modified hemoglobin solutions needs to be improved, our data show that hemoglobin solutions can be effective at reducing exposure to allogeneic blood for elective surgery.

Vancomycin vs tobramycin elution from polymethylmethacrylate: an in vitro study.

We fabricated batches of cement containing 0.5 gm, 1.0 gm, and 2.0 gm vancomycin and one with 1.0 gm tobramycin and shaped them into cylinders. They were immersed into 0.5 L of normal saline and the fluid volume was changed daily. Samples of fluid were obtained on days 1, 2, 3, 5, 7, 14, and 28. All fluid samples had antibiotic assays performed to quantitate the amount of elution for vancomycin or tobramycin. Vancomycin elution from PMMA occurred under our study conditions in similar quantities to that measured for tobramycin controls. Vancomycin-loaded PMMA cement may have a clinical role in the treatment of musculoskeletal sepsis caused by gram-positive bacteria, particularly if organisms resistant to the usual antibiotic agents are identified.

Juxta-articular osteoid osteoma.

Osteoid osteomas that arise at the end of a long bone, within the insertion of the joint capsule (juxta-articular, intra-articular), may cause misleading clinical, radiographic, and histologic findings, resulting in unnecessary diagnostic tests and a delay in definitive treatment. To clarify optimum diagnostic procedures, we reviewed 20 cases of juxta-articular osteoid osteomas and found a mean delay from presentation to correct diagnosis of 24 months. Plain radiographs were either negative or showed only secondary changes. A periosteal reaction and proliferative synovitis with chronic inflammation was common, which could be misinterpreted as rheumatoid arthritis. Optimum diagnostic procedures were a bone scan followed by plain tomograms and an excisional biopsy of the nidus.

Phase II Trial of Liposomal Doxorubicin (Doxil®) in Advanced Soft Tissue Sarcomas

AbstractPurpose: To assess the objective response rate, toxicityexperienced, progression-free survival, and overall survival ofpatients with previously untreated advanced soft tissue sarcomastreated with a liposomal doxorubicin formulation (Doxil). Methods: Patients with metastatic or recurrent soft tissuesarcoma who had received no prior chemotherapy for advanceddisease were treated with liposomal doxorubicin (Doxil) accordingto a two stage accrual design. Doxil was administered at 50mg/m2 every 4 weeks. A total of 15 patients were treated andare evaluable for response and toxicity. Results: The male/female ratio was 7/8, the median age was60 years (34–75) and the ECOG performance status was 0-1 in>90% of patients. Leiomyosarcoma (7/15) and malignant fibroushistiocytoma (2/15) were the most common histologic diagnoses.No objective responses were observed in the 15 evaluablepatients. No lethal toxicity occurred. Grade 3–4 leukopenia orneutropenia were reported in 3/15 (20%) patients. Grade 3mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15(7%) patients respectively and seemed more severe in olderpatients. The median time to progression was 1.9 months (range0.9–6.2). Twelve patients have now died. The Kaplan-Meierestimate of median overall survival is 12.3 months. As called forin the study design, accrual was terminated because no responseswere obtained in the first 15 patients. Conclusion: Though well-tolerated, Doxil given accordingto this dose and schedule to patients with advanced soft tissuesarcoma had no significant therapeutic activity. A correlationbetween older age and skin/mucosal toxicity of Doxil is suggestedin this study but needs confirmation. Future investigations ofDoxil in soft tissue sarcomas should use a different schedule anddose.

Osteosarcoma of the Hand

Two cases of osteogenic sarcoma in the hand are reported, with a discussion of the literature.

EFFECT OF DIASPIRIN CROSSLINKED HEMOGLOBIN (DCLHb HemAssist™) DURING HIGH BLOOD LOSS SURGERY ON SELECTED INDICES OF ORGAN FUNCTION *

Background: The safety of the hemoglobin based oxygen carrier diaspirin crosslinked hemoglobin (DCLHb) has been reported only in the low (50–200 mg/kg) dose range[Przybelski, R.J.; Daily, E.K.; Kisicki, J.C.; Mattia-Goldberg, C.; Bounds, M.J.; Colburn, W.A. Phase I study of the safety and pharmacologic effects of diaspirin crosslinked hemoglobin solution. Crit. Care Med. 1996, 24 (12), 1993–2000, Bloomfield, E.; Rady, M.; Popovich, M.; Esfandiari, S.; Bedocs, N. The use of diaspirin crosslinked hemoglobin (DCLHb™) in post-surgical critically ill patients. 1996, 95, (3A), A220.]. We conducted a randomized prospective open-label trial of DCLHb and packed red blood cells (PRBCs) in high-blood loss surgical patients to show the effect of 750 ml DCLHb (approximately 1000 mg/kg) on selected indices of organ function. Method: After institutional approval, 24 patients scheduled to undergo elective orthopedic or abdominal surgery, were randomized to receive either PRBCs or 10% DCLHb within 12 hours after the start of surgery. Patients with renal insufficiency, abnormal liver function, severe coronary artery disease (CAD) and ASA physical status≥IV were excluded. The anesthetic technique was left to the judgment of the anesthesiologist. Autologous pre-donation and intraoperative blood conservation techniques were utilized as appropriate. The indications for blood transfusion were individualized on disease state, stage of surgery, and plasma Hb concentration. Laboratory studies were obtained preoperatively and up to 28 days postoperatively. Patients were observed daily for development of jaundice, hematuria, nausea, vomiting, gastrointestinal discomfort, cardiac, respiratory, and infectious complications. Organ effects were assessed with urinalysis, creatinine clearance, electrocardiogram (ECG), and a panel of blood and serum laboratory tests. Results: The dose of DCLHb administered ranged from 680–1500 mg/kg (mean=999 mg/kg). Estimated blood loss was 27±13 ml/kg and 31±15 ml/kg in the control and DCLHb groups, respectively. Fewer PRBCs (1.9±1.2 vs. 3.4±2.4 units, P=0.06) were transfused to DCLHb patients on the operative day although this difference was no longer apparent later on. In the DCLHb group, 4/12 patients avoided any allogeneic PRBC transfusion vs. none in the control group (P=0.09). Systolic, diastolic and mean blood pressure increased moderately after DCLHb for a period of 24–30 hours. There were no occurrences of cardiac ischemia, myocardial infarction, stroke, or pulmonary edema, by clinical or laboratory parameters up to the 28th postoperative day (POD). Seven of 12 (58%) DCLHb patients had yellow skin discoloration vs. none in the PRBC group (P<0.01). Two of four non-urologic surgery patients developed asymptomatic postoperative hemoglobinuria after DCLHb. Creatinine clearance was unchanged postoperatively. Because of hemoglobin interference, bilirubin, γ-glutamyl transferase (GGT), and amylase could not be measured reliably on POD1; on POD2, amylase was transiently elevated to 3 times ULN along with mild elevations of bilirubin, transaminases and BUN. Mean total creatine phoshokinase (CPK) peaked at 8 times the upper limit of normal (ULN) in the DCLHb group, compared with less than twice ULN for controls. Three DCLHb patients had prolonged ileus. Two of these patients had postoperative hyperamylasemia, one of whom developed mild pancreatitis. DCLHb did not affect white blood cell count or coagulation tests. Conclusion: Administration of approximately 1000 mg/kg DCLHb was associated with transient arterial hypertension, gastrointestinal side effects, laboratory abnormalities, yellow skin discoloration, and hemoglobinuria. These observations point to opportunities for improvement in future synthetic hemoglobin design.

Periosteal Ewing's sarcoma

Ewings sarcoma is a small cell malignant tumor that usually arises in the medullary cavity of bone. Less frequently, it originates in soft tissue and may secondarily invade underlying bone. The origin of Ewings sarcoma in a periosteal location without extension into either the bone or adjacent soft tissue has not been clearly documented. Other malignant tumors of bone (e.g., osteosarcoma) appear to have a somewhat better prognosis when confined between periosteum and bone. The case of a patient with a periosteal Ewings sarcoma who received a radical excision and postoperative chemotherapy and who is without evidence of disease with over 2 years follow‐up is reported.

Intraneural lipoma of the sciatic nerve.

A large, well-encapsulated intraneural lipoma occurred within the sciatic nerve of a 34-year-old woman. In a review of the literature, significant differences were noted between the well-encapsulated and the diffusely infiltrative lipofibromatous hamartoma types of intraneural lipomas. The average age at the time of appearance of the well-encapsulated type is 45 years, with female predominance, while the infiltrative type arises in a younger age group (average age, eight years) with no sexual predominance. To avoid a recurrence, total excision is recommended in cases of the well-encapsulated type. Attempts to excise the diffusely infiltrative type are likely to fail.

Papillary clear cell adenocarcinoma of the groin arising from endometriosis.

A 67-year-old woman presented with rapidly enlarging right anterior thigh mass. Clinical impression was of a primary sarcoma, but the histologic analysis of an incisional biopsy specimen showed adenocarcinoma with clear cell differentiation. Initially thought to be a metastasis, the malignant tumor appears to have arisen from extraabdominal endometriosis of the right groin. This case shows clinical, radiographic, and histologic findings that may help the orthopaedic surgeon recognize an unusual complication of extrapelvic endometriosis.

ADJUVANT BRACHYTHERAPY IN THE TREATMENT OF SOFT-TISSUE SARCOMAS

For many patients with STS, administering adjuvant radiation treatments in the form of interstitial brachytherapy provides an excellent alternative to a protracted course of EBRT. Ideal patients are those with intermediate- or high-grade tumors amenable to en bloc resection. Attractive features of this approach include an untainted pathologic specimen, expeditious completion of treatment, reduction in wound complications, and improved functional outcome. Brachytherapy can permit definitive reirradiation by tightly localizing the high dose radiation exposure. It is also useful in patients who are known to have or be at high risk of metastatic disease, for whom the rapid completion of local treatment allows systemic therapy to begin quickly. Introduction of HDR techniques has shifted the delivery of brachytherapy from inpatient solitary confinement to an outpatient setting. Early reports using HDR brachytherapy for treatment of adult and pediatric STS are quite encouraging. The clinical equivalence between hyperfractionated HDR schedules and traditional LDR techniques is gaining acceptance.