Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:² preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.     

Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.

Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.     

Nephrectomy during operative management of retroperitoneal sarcoma

Background: Complete resection of a retroperitoneal sarcoma often requires removal of adjacent organs. In this study we evaluated the role of nephrectomy during operation for retroperitoneal sarcoma. Methods: Between July 1982 and July 1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons for nephrectomy, degree of sarcomatous renal involvement, and survival were retrospectively analyzed. Results: Fifty-four patients (72%) underwent nephrectomy during the initial resection, and 21 (28%) during a resection of a recurrent or persistent tumor. The most common reason for nephrectomy was total encasement by sarcoma (n=40; 53%), followed by dense adherence of the tumor to the kidney (n=21; 28%), and the direct invasion of the kidney by tumor (n=2; 3%). Pathology demonstrated an absence of kidney invasion in the majority of cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%), renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75 (3%) of cases. There were no significant differences in survival based on degree of sarcoma involvement of the kidney, tumor grade, or whether the resection was for primary or recurrent disease. The 53 patients who underwent a complete gross resection of all tumor had a significantly improved long-term survival compared to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p<0.001). Conclusions: Decisions for concomitant nephrectomy during resection of retroperitoneal sarcoma should be based on whether this maneuver will provide a complete resection of all gross tumor, in which case the long-term disease-free survival of 50% is comparable to the reported 5-year survival of all patients with retroperitoneal sarcoma who are completely resected. Presented at the 49th Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Simultaneous Pulmonary Leiomyosarcoma and Leiomyoma in Pediatric HIV Infection

The case of a 7-year-old girl with acquired immunodeficiency syndrome treated for 5 years with AZT and intravenous gamma globulin is reported. Shortly before her demise she developed a pulmonary leiomyosarcoma and leiomyoma. Does prolonged survival in pediatric acquired immune deficiency syndrome increase the incidence of secondary malignancies?     

Comparison between continuous and intermittent infusion regimens of cimetidine in ulcer patients

The relative effectiveness of intermittent infusions and primed continuous infusions of cimetidine in the maintenance of intragastric pH greater than or equal to 4.0 was evaluated in a double-blind crossover trial in 26 patients who had active or healed gastroduodenal ulcers. During the intermittent phase, each patient received 300 mg cimetidine intravenously every 6 hours. During the continuous infusion phase, each patient was given a continuous infusion of 37.5 mg cimetidine per hour, preceded by a priming dose of 300 mg cimetidine that was given for 15 minutes. Intragastric pH was monitored continuously. During the last 12 hours of the study, the continuous infusion regimen provided 20% more time in which the pH was more [corrected] than 4.0 with 25% less medication than did the intermittent infusion regimen.     

A kinetic study of leucine metabolism in severely burned patients. Comparison between a conventional and branched-chain amino acid-enriched nutritional therapy.

A cross-over design study was used to examine the metabolic consequences of enteral feeding for 48 to 96 hours with either a branched-chain amino acid (BCAA)-enriched (44% BCAA) or a conventional egg protein formulation in 12 severely burned adult patients. A stable isotope labeled leucine (L-1-13C-leucine) tracer approach was used to measure leucine flux and oxidation and to estimate rates of whole body protein synthesis and breakdown. Additionally, 15N2-urea and 6,6-2H-glucose were administered to assess the status of urea and glucose kinetics with these two nutritional treatments. Average patient age was 54 years, and average burn surface area was 36%. Studies were conducted at an average of 25 days postburn. Leucine flux and oxidation were significantly (p less than 0.01, by paired t-test) elevated with BCAA feeding as compared to the egg protein formulation. However, there were no significant differences in the rates of leucine incorporation into, or release from, proteins (p greater than 0.05) between the two dietary periods. Mean rates of body protein synthesis and breakdown for each diet were about twice the rates reported for healthy young adults. Apparent nitrogen balance measurements were not statistically different (p greater than 0.1) between the two diet periods. Furthermore, urea and glucose kinetics failed to show significant differences between the two diet periods. It appears from these results that the major consequences of increased intake of leucine from the BCAA formula is an enhanced rate of leucine oxidation. In conclusion, (1) the availability of BCAAs is not rate-limiting for enhanced protein synthesis in burn patients, and (2) the use of enriched BCAA formulas in burn therapy does not appear to offer advantages over a routinely used enteral egg protein formula, at least based on the present determinations.     

In situ hybridization of prostate-specific antigen mRNA in human prostate.

Prostate-specific antigen (PSA) mRNA was detected by in situ hybridization utilizing a 428 base pair [35S]-labelled cDNA probe from the 3' noncoding region of the PSA gene. Thirty six fresh surgical specimens were collected from patients undergoing radical retropubic prostatectomy for carcinoma of the prostate. Quantitative analysis of the levels of PSA mRNA in both the benign and malignant tissues was performed using an IBAS 2000 Image Analysis System. The results of this study demonstrated that there is a significant decrease in the expression of PSA mRNA in the carcinoma tissue when compared to the benign epithelium. The average binding (number of silver grains/1 x 10(4) microns. 2) for 20 specimens of malignant epithelium was 475 +/- 161 and 586 +/- 140 for 16 specimens of benign epithelium (p less than 0.05). Eleven patients had both benign and malignant tissue from the same surgical specimen available for study. From these paired specimens, the PSA mRNA expression was also significantly reduced in the malignant epithelium when compared to the benign epithelium, 445 +/- 162 and 588 +/- 135 respectively (p less than 0.005). The PSA protein was detected using a monoclonal antibody to PSA with an immunohistochemical staining technique. The PSA protein expression paralleled the expression of the PSA mRNA in the majority of the tissue sections. Many of the tumor specimens showed a heterogeneous expression of PSA, whereas all of the benign epithelium had a uniform high level of PSA expression. In conclusion, PSA mRNA and protein are located only within the glandular epithelial tissue, the expression of PSA protein parallels that of the PSA mRNA, and both the PSA protein and PSA mRNA are significantly decreased in the malignant epithelium when compared to benign prostatic epithelium.