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Biomedical subjects

R E Pollock

Publications and source records attributed to R E Pollock.

At least 55 records · Page 3Linked to original sources

Preoperative chemotherapy for stage IIIB extremity soft tissue sarcoma: long-term results from a single institution.

PURPOSE: To review a single institution's long-term results with doxorubicin-based preoperative chemotherapy for American Joint Committee on Cancer (AJCC) stage IIIB extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: The records of all patients with AJCC stage IIIB extremity STS treated with preoperative chemotherapy between 1986 and 1990 at The University of Texas M.D. Anderson Cancer Center were reviewed to assess rates of response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Seventy-six patients with stage IIIB disease received preoperative chemotherapy. The median sarcoma size was 10 cm. Seventy-two patients (95%) had tumors located deep to the muscular fascia. Most patients received a median of three preoperative cycles of doxorubicin and dacarbazine (ADIC), cyclophosphamide and ADIC (CyADIC), or other doxorubicin-based regimens. Radiographic response rates were as follows: complete response (CR), 9%; partial response (PR), 19%; minor response, 13%; stable disease, 30%; and progression, 30%. The overall objective major response rate (CRs plus PRs) was 27%. At a median follow-up time of 85 months, 5-year actuarial rates of LRFS, DMFS, DFS, and OS with 95% confidence intervals (CIs) were 83% (CI, 73% to 94%), 52% (CI, 41% to 66%), 46% (CI, 35% to 60%), and 59% (CI, 48% to 72%), respectively. Comparison of responding patients (CRs plus PRs) and nonresponding patients did not show any significant differences in LRFS, DMFS, DFS, or OS. CONCLUSION: Preoperative doxorubicin-based chemotherapy was associated with response, DFS, and OS rates similar to those observed in randomized postoperative chemotherapy trials. Responding patients had rates of LRFS, DMFS, DFS, and OS comparable to those of nonresponders.

Adolescent↗

The National Cancer Data Base report on soft tissue sarcoma.

BACKGROUND: Discernible improvements have taken place in soft tissue sarcoma patient survivorship and quality of life over the past 20 years, with overall 5-year survival currently at approximately 50%. Shifts in treatment have taken place over the past decade, from single-modality treatment involving radical surgery to sophisticated limb-salvage strategies combined with radiation therapy and protocol-administered chemotherapy. METHODS: To identify patterns of treatment and outcome, all soft tissue sarcoma cases diagnosed in 1988 and 1993 as recorded in the National Cancer Data Base were analyzed on the basis of histology and anatomic site. RESULTS: There was an increase in sarcomas originating in the pleura with a concurrent increase in mesotheliomas. A shift toward more advanced disease was also noted. Limb-sparing surgical procedures are now standard. However, it appears from stage subset analysis that many Stage II and III patients are undertreated due to lack of multimodality therapy usage. CONCLUSIONS: Use of pretreatment multimodality planning conferences will increase the likelihood that stage-appropriate combinations of surgery, radiation therapy, and chemotherapy will be used. In turn, election of multimodality approaches should increase the possibility of improved overall and disease free survival in the future.

Databases, Factual↗

Soft tissue sarcoma metastasis from clonal expansion of p53 mutated tumor cells.

Although soft tissue sarcoma has a high incidence of p53 mutations, it is not clear if such alterations facilitate tumor growth and metastasis. In this study, fresh autologous normal lymphocytes, normal muscle, primary and metastatic sarcoma tissues from a single synovial sarcoma patient were examined for p53-related alterations that potentially associated with sarcoma tumor development and metastasis. Normal tissues contain two wild-type p53 alleles. Primary sarcoma had one chromosome 17p p53 allelic deletion without apparent p53 mutation in the other allele. However, metastatic tumor had deletion of one p53 allele with an exon 5 codon 135 missense mutation in the other allele. This p53 gene point mutation in the metastasis was associated with the production of mutated p53 protein. A small clone of cells harboring the identical p53 gene point mutation was identified in the primary tumor using mutant allele specific PCR amplification, albeit at levels much less than in the metastatic sarcoma. This single patient example indicate that soft tissue sarcoma metastasis can develop from clonal expansion of primary tumor cells bearing p53 mutations.

Base Sequence↗

Malignant fibrous histiocytoma in children.

Because malignant fibrous histiocytoma (MFH) rarely occurs in children, the natural history of this tumor and prognostic factors predictive of outcome have not been well described. The charts of all pediatric patients with MFH seen at M.D. Anderson Cancer Center were reviewed with respect presentation, treatment, and outcome, in an attempt to determine prognostic factors that are predictive of survival. Forty-four pediatric patients were identified. Extremities were the most common tumor site (31 of 44 patients). Five patients presented with angiomatoid histology subtype; all subsequently survived. The estimated 5-year survival rate was 85% for clinical group I patients, 87% for clinical group II, 53% for clinical group III, and 0% for clinical group IV. The estimated 5-year survival rate was 95% for patients with tumors of less than 5 cm in diameter and 45% for those with larger tumors. Overall, the estimated 5-year survival rate was 71%. Significant prognostic factors found to affect survival (by univariate analysis) were clinical group, tumor size, and recurrence. Gender and race were not significant predictors. The use of chemotherapy and radiation was not found to improve the chance of survival, but this most likely reflected the more frequent use of adjuvant therapy in patients with unresectable or high-grade tumors. Although adequate surgical resection continues to be the most effective treatment, investigation of adjuvant chemotherapy and radiation therapy on protocol is warranted.

Adolescent↗

Human peri-tumoral and lung fibroblasts produce paracrine motility factors for recently established human sarcoma cell strains.

Paracrine motogenic cytokines secreted by normal cells can stimulate metastatic cell invasion. For example, human fibroblasts secrete hepatocyte growth factor/scatter factor (HGF/SF), which stimulates paracrine migration of epithelial and certain carcinoma cells, and migration-stimulating factor (MSF), which stimulates autocrine migration of fibroblasts from certain breast carcinomas. We found that human peri-tumoral and lung fibroblasts secrete motility-stimulating activity for several recently established human sarcoma cell strains. Motility of lung metastasis-derived SYN-I sarcoma cells was preferentially stimulated by human lung and peri-tumoral fibroblast motility-stimulating factors (FMSFs). FMSFs were non-dialyzable, susceptible to trypsin and sensitive to dithiothreitol. Cycloheximide inhibited accumulation of FMSF activity in conditioned medium; however, addition of cycloheximide to the migration assay did not significantly affect motility-stimulating activity. Purified HGF/SF, rabbit anti-hHGF and RT-PCR analysis of peri-tumoral and lung fibroblast HGF/SF mRNA expression indicated that FMSF activity was unrelated to HGF/SF. Partial purification of FMSF by gel exclusion chromatography revealed several peaks of activity, suggesting multiple FMSF molecules or complexes. Since human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), FMSF may play a role in this process independent of HGF/SF.

Base Sequence↗

Ethics of research training for NIH T32 surgical investigators.

As part of the revised curriculum of the NIH T32 Training Grant mechanism, 6 hr of formal instruction in ethics of research are now required. We therefore implemented a four-session seminar (6 hr total time) structured around assigned readings, didactic presentations, and group discussions. The objective of this research project was to assess whether this new program provided our trainees with a framework for ethical conduct in research. Twelve trainees completed the ethics course; 8 trainees who had not yet taken the ethics course served as a control group. All trainees answered a 72-item questionnaire of our own design that examined a variety of issues in research ethics. We compared the responses of seminar participant and nonparticipant groups using the Fisher exact test and Student t test for nominal and ordinal data, respectively. Both groups of trainees perceived that too much emphasis was placed on quantity rather than quality of publications. Both groups felt that this pressure emanated from department chairmen rather than laboratory mentors (P < 0.0001). In contrast to these shared perceptions, the two groups demonstrated many differences in their comprehension of research ethics. For example, compared to the controls, trainees who participated in the ethics course believed that they could define potential NIH standards for data storage and research mentorship (P < 0.05), understood gratuitous manuscript authorship (P < 0.05), were comfortable in dealing with outlier or discordant data (P < 0.10), and, most pertinently, were fully prepared to seek third-party input into an ethical dilemma involving their own work (P < 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Experimentation↗

Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone.

Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT) in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at M(r) 121,000, 92,000, and 72,000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.

Bone Neoplasms↗

Soft-tissue sarcomas of the shoulder girdle: factors influencing local recurrence distant metastases, and survival.

BACKGROUND: Prognostic factors and the role of radiotherapy have not been well characterized for soft-tissue sarcomas (STS) of the shoulder girdle. METHODS: The cases of 70 patients with primary shoulder STS were reviewed for the following information: size, grade and histology of tumors, extent of resection, and use of adjuvant radiotherapy. The influence of these factors on local disease-free survival (LDFS), distant disease-free survival (DDFS), and overall survival (OS) rates was analyzed using univariate analysis. RESULTS: With a median follow-up of 108 months, the overall 5- and 10-year survival rates for patients with shoulder girdle STS were 82% and 80%, respectively, whereas the 5-year disease-free survival rate was 63%. There were 25 (35%) tumor recurrences: 12 (17%) distant and 13 (18%) local regional. Tumors > 5 cm in size were associated with a significantly decreased 5-year OS rate compared with lesions < 5 cm, and high-grade tumors were associated with significantly decreased DDFS and OS rates. Because most of the patients who underwent amputation had large, high-grade tumors, they had significantly decreased 5-year DDFS and OS rates compared with wide local excision. Radiotherapy produced a significant improvement in LDFS rates, particularly in patients with tumors > 5 cm in size. CONCLUSIONS: The results indicate that both tumor size and grade are important prognostic factors in shoulder girdle STS. Adjuvant radiotherapy should be considered in large tumors to improve the LDFS and to decrease the need for radical ablative surgery.

Adolescent↗

Vascular access by physician assistants: evaluation of an implantable peripheral port system in cancer patients.

PURPOSE: To determine the ability of a physician assistant (PA) to insert, in an ambulatory setting, a peripheral subcutaneous implanted vascular-access device (VAD) and to evaluate the ability to transfer this training to a second PA. We also evaluated the performance and complications associated with this new device. PATIENTS AND METHODS: The Peripheral Access System (PAS) Port catheter system (Sims-Deltec Inc, St Paul, MN) was inserted in patients who required long-term (> 3 months) vascular access for infusion therapy. RESULTS: The first PA (PA-1) successfully inserted 57 of 62 devices (92%) after gaining experience with the technique in 10 patients (success rate, five of 10 [50%]; P = .003). The second PA (PA-2) was successful in eight of 10 initial attempts (80%) and 25 of 30 overall (83%). Complications were few and limited to phlebitis, thrombosis, and a low infection rate (0.2 per 1,000 catheter days). CONCLUSION: PAs can be taught to insert a peripheral subcutaneous implanted VAD. This technique is transferable from one PA to another, and the device studied is appropriate for outpatient VAD programs.

Adolescent↗

Surgical management of primary soft tissue sarcoma.

Few areas in oncology more clearly illustrate the need for multidisciplinary management than the soft tissue sarcoma problem. Using this approach has led to limb preservation with survival results at least equivalent to those for amputations. This achievement has dramatically improved the quality of life and overall clinical outcome for patients with this disease. In the future, improved understanding of the biology of this disease may broaden our therapeutic options. Meanwhile, a detailed understanding of the surgical possibilities will enhance the multimodality care that can be offered by the teams of clinicians managing patients suffering from this disease.

Amputation, Surgical↗

Biologic distinctions and therapeutic implications of sarcomatoid metaplasia of epithelial carcinoma of the breast.

BACKGROUND: Malignant sarcomatoid metaplasia of epithelial carcinoma of the breast (carcinosarcoma) is diagnosed at an annual rate of two cases per 107 women in the United States of America. It seems that these tumors behave differently than other carcinomas or sarcomas of the breast. STUDY DESIGN: The University of Texas M. D. Anderson Cancer Center experience (1947 to 1991) treating 50 patients (mean age of 50 years, range of 25 to 76 years) was retrospectively reviewed. The five-year overall survival and disease-free survival rates were compared and prognostic factors were identified. RESULTS: The overall survival rate of 43 percent was lower than had been expected for carcinoma of the breast. No patient with stage IV disease survived five years. Tumor size and stage at diagnosis had the strongest impact on outcome. The impact of axillary lymph node status on prognosis was less than expected. Hormonal receptor levels were positive in only 12.5 percent of the tumors tested. Mastectomy with adjuvant chemotherapy or radiotherapy, or both, was superior to mastectomy alone and to wide local excision with or without adjuvant therapy, particularly for patients with stage II disease. If complete surgical resection is possible, the surgical approach for treatment of recurrent disease is better than any other modality. CONCLUSIONS: Carcinosarcoma behave biologically differently than conventional carcinoma of the breast in that sarcomatoid characteristics dominate the clinical course. These biologic distinctions should direct the treatment toward a multimodality approach that includes mastectomy and sarcoma-oriented adjuvant chemotherapy and radiotherapy.

Adult↗

Soft-tissue sarcoma of the extremities. MR appearance of post-treatment changes and local recurrences.

MR imaging has the potential to provide valuable insights into intratumoral changes following preoperative therapy and has proven beneficial in the diagnosis of recurrent soft-tissue sarcoma of the extremities and differentiation of recurrence from postsurgical/postradiation changes. As advances occur in surgical and adjuvant treatment programs, further refinements of qualitative and quantitative MR imaging parameters should continue to enhance the role of MR imaging in the post-treatment evaluation of patients with soft-tissue sarcoma of the extremities.

Chemotherapy, Adjuvant↗

Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas.

BACKGROUND: Limb-sparing surgery for soft tissue sarcomas of the extremities may result in microscopically positive surgical margins. The consequences of these microscopically positive margins are unknown. We have analyzed the influence of surgical margins on local disease control and overall survival in patients with extremity soft tissue sarcomas who received preoperative radiation therapy followed by limb-sparing surgery. METHODS: Ninety-five consecutive patients with intermediate and high grade extremity sarcomas who received preoperative radiation therapy and limb-sparing surgery were identified from a soft tissue sarcoma data-base. The clinical outcome of 24 patients who had microscopically positive surgical margins was compared with that of 71 patients who had clear surgical margins. RESULTS: Multivariate statistical analysis revealed that patients with microscopically positive surgical margins or intraoperative tumor violation had an increased risk for local failure. High grade, large size, and intraoperative violation of the tumors were associated with decreased overall survival. However, neither the presence of a positive surgical margin nor the occurrence of a local failure adversely affected overall survival. CONCLUSIONS: Achieving negative surgical margins in patients with intermediate and high grade extremity sarcomas enhances local disease control but does not measurably improve overall survival. These data should be factored into patient management decisions in cases where the goal of achieving clear surgical margins requires amputation or the significant functional compromise of the extremity.

Actuarial Analysis↗

Diagnosing intramuscular myxoma by fine-needle aspiration: a multidisciplinary approach.

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (non-plexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma.

Adult↗