Training for careers in academic surgical oncology: the future is bright.
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Academic Medical Centers↗
Biomedical subjects
R E Pollock
Publications and source records attributed to R E Pollock.
Laparoscopic splenectomy in patients with hematologic malignancies.
BACKGROUND: Although laparoscopic splenectomy (LS) for benign hematologic disease is well accepted, its role in hematologic malignancies is not clearly defined. This study examined the efficacy and feasibility of LS for hematologic malignancies. METHODS: Records were reviewed from patients who underwent LS at two university hospitals. Charts from 77 open splenectomies for malignancy (OM) during the same period were also reviewed. RESULTS: Fifty-three patients underwent LS, 22 for hematologic malignancies (LM) and 31 for benign hematologic disorders (LB). Median splenic weight was greater in the LM group (930 g) than in the LB group (164 g, P = 0.001). LM was associated with longer operations and greater blood loss than was LB. LM had a 41% conversion rate. Morbidity, mortality, and transfusion rates were similar. Median hospital stay was shorter for LM (4 days) than for OM (6 days, P = 0.001). CONCLUSIONS: LS is feasible in hematologic malignancies but is associated with increased operative time and blood loss and a high conversion rate. Morbidity and mortality, however, was similar. Shorter hospital stays for LM compared with OM may translate into earlier recovery and initiation of antineoplastic therapy.
Adult↗
Role of radiotherapy in sarcoma of the breast--a retrospective review of the M.D. Anderson experience.
BACKGROUND: The role of adjuvant radiotherapy for sarcoma of the breast, based on local extension of disease and patterns of failure, remains undefined because of the rarity of the disease presentation. METHODS: Fifty-nine cases of soft tissue sarcoma of the breast were retrospectively reviewed. Cystosarcoma phylloides was excluded from analysis. Surgical intervention consisted of segmental resection (n = 16) or mastectomy (n = 38); five patients underwent excisional biopsy. Adjuvant radiotherapy was administered in four patients following segmental resection and in 13 patients after mastectomy. Doses totaled 50 Gy in the majority of patients, and conventional criteria and radiotherapy techniques for adjuvant breast irradiation were used. RESULTS: None of the dissected axillary nodes contained metastatic tumor on pathologic review. Patterns of failure were evaluated. Tumor size (P < 0.03) and surgical margins (P < 0.002) were predictive of local failure (LF). Due to limited patient numbers, no statistical significance was identified with any treatment modality. Following mastectomy alone, LF occurred in 13 patients (34%) versus the 13% rate of LF with mastectomy and radiotherapy (P = NS). Distant metastases developed concurrently with the two local failures in the group that underwent mastectomy and radiation. After segmental mastectomy, LF occurred in 3 cases (25%) concurrent with distant metastases: no LF were noted after segmental mastectomy and radiation (P = 0.27). For all treatment groups, local recurrences were characterized as multiple and involved the chest wall. Local failure occurred in 60% of patients with positive surgical margins who did not receive adjuvant irradiation. Irrespective of surgical margins, over 75% of local recurrences developed among patients treated by surgery alone. CONCLUSIONS: The role of radiotherapy for breast sarcoma remains undefined due to the rarity of this disease presentation. This retrospective review failed to demonstrate a statistical benefit for the administration of adjuvant irradiation in sarcoma of the breast, probably because of limited patient numbers. Because large tumor size and positive surgical margins incur a higher risk for LF, radiotherapy is probably indicated in these cases. Axillary dissection obligates the radiotherapist to treat the axilla in order to include all tissues in the surgical bed, and should be avoided to reduce potential treatment related morbidity. Established therapeutic principles and techniques used for both soft tissue sarcoma and breast cancer should continue to be applied.
Adolescent↗
Resectable recurrent extremity sarcomas: is there a role for re-irradiation?
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Adult↗
Staging and prognostic factors in soft tissue sarcoma.
Significant advances have been made in the understanding of clinicopathologic prognostic factors for soft tissue sarcoma over the past decade. Foremost among these advances is an improved ability to recognize the subset of patients at high risk for recurrent disease based on clinicopathologic data available at the time of initial presentation. Progress has also helped to elucidate specific molecular factors that have independent prognostic significance. This review outlines the updated American Joint Committee on Cancer staging system for soft tissue sarcoma and summarizes the available data on traditional clinicopathologic and molecular prognostic factors.
Humans↗
Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.
PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.
Adolescent↗
Hemangiopericytoma: a 20-year single-institution experience.
BACKGROUND: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to evaluate the long-term outcome of a consecutively treated patient cohort with hemangiopericytoma. METHODS: The study involved 36 adult patients (older than 16 years) with hemangiopericytoma treated at The University of Texas M. D. Anderson Cancer Center between July 1975 and July 1995. Data on clinicopathologic parameters, surgical treatment, adjuvant therapy, disease recurrence, and survival were obtained from a review of medical records. RESULTS: The median follow-up was 57 months. Twenty-eight patients (78%) underwent complete and potentially curative resection of their primary disease. Of the nine patients (32%) who had local recurrences, four (57%) had epidural tumors and three (43%) had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were associated with a significantly prolonged local recurrence-free survival compared to tumors at nonextremity anatomic sites (P <.05). Ten patients had recurrences at distant sites. Of the 13 patients who experienced any form of disease recurrence, four had recurrences after a disease-free interval of more than 5 years. The 5-year actuarial survival rate for the entire group of 36 patients was 71%. Noncurative surgical treatment (P=.007) and development of distant metastatic disease (P=.013) were associated with shortened survival. CONCLUSION: Extended survival is common in hemangiopericytoma patients treated with curative intent. However, local and distant recurrences may occur after a prolonged disease-free interval, emphasizing the need for long-term follow-up. Retroperitoneal and meningeal tumors were associated with higher local recurrence rates; therefore, adjuvant therapies should be considered and evaluated for tumors at these sites.
Adult↗
Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection.
BACKGROUND: Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND. METHODS: Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively. RESULTS: There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87). CONCLUSIONS: We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.
Adult↗
Cytotoxic effects of sphingolipids as single or multi-modality agents on human melanoma and soft tissue sarcoma in vitro.
We evaluated the cytotoxic effects of a cell-permeable ceramide (Cer), N-hexanoyl-D-sphingosine (C6-Cer) and of two related sphingoid bases, sphingosine (So) and dihydrosphingosine (sphinganine; Sa) on human melanoma cell lines and on soft tissue sarcoma lines recently established from fresh surgical biopsy specimens. These cell lines ranged from high susceptibility (939 melanoma) to strong resistance (A2058 melanoma and all three sarcomas) to tumour necrosis factor (TNF), an inducer of elevated intracellular Cer levels. However, all the cell lines demonstrated a dose-dependent susceptibility to C6-Cer with protracted cytotoxic kinetics, with the C8161 melanoma being the most sensitive and A2058 the least. Protein kinase C (PKC) antagonizes Cer-dependent apoptosis, and chelerythrine chloride, So and Sa, which inhibit PKC, caused extremely rapid cytotoxicity of melanoma cell lines, irrespective of their relative sensitivity to C6-Cer. So-mediated cytotoxicity was extensive even after only 90 min of treatment, within the time frame of limb perfusion. So and Sa only slightly potentiated the cytotoxic responses to TNF, C6-Cer or melphalan. Sphingolipid-driven intracellular pathways may offer opportunities for therapy of these tumours.
Alkaloids↗
Epidermal growth factor receptor and insulin-like growth factor-I receptor expression and function in human soft-tissue sarcoma cells.
Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) receptors are implicated in the development and progression of several malignancies including osteogenic and soft tissue sarcomas (STS). To determine a role for ligand-mediated receptor activation in sarcoma progression, the relative expression and function of EGF-R, IGF-I-R, and several other molecular determinants implicated in the progression of mesenchymal neoplasms were evaluated in human sarcoma cells established from surgical specimens of primary and metastatic tumors. mRNA blot analyses demonstrated the expression of c-Met, p53, and MDM2-specific transcripts. Western blot analyses confirmed the production of high levels of p53 protein; however, minimal levels of MDM2 and c-Met proteins were detected. Analysis of STS cells #23, #26, and #50 originating from an unclassified sarcoma lung metastasis, a malignant fibrous histiocytoma lung metastasis, and a dedifferentiated chondrosarcoma, respectively demonstrated high steady-state levels of EGF-R and IGF-I-R mRNA transcripts and protein correlating with receptor-specific tyrosine kinase activity and autophosphorylation in response to ligand. Treatment of these STS cells with EGF resulted in a >5 fold increase in DNA synthesis and mitogenesis compared with untreated controls. In contrast, treatment with IGF-I showed a variable STS growth response correlating with the origin of the tumor. These data support the involvement of EGF-R and IGF-I-R in the growth and metastasis of human soft tissue sarcoma and may offer new targets for therapeutic intervention in the management of this disease.
Blotting, Western↗
Infrequent mutation of the p16/MTS1 gene and overexpression of cyclin-dependent kinase 4 in human primary soft-tissue sarcoma.
The pl6INK4a/MTS1 (p16) gene encodes a specific inhibitor of cyclin-dependent kinase (CDK)4 and CDK6. The p16 gene is frequently mutated or deleted in many types of cancer cell lines as well as in certain types of primary tumors. p16 knockout mice are viable but predisposed to sarcoma and B-cell lymphoma. To investigate the role of p16 in human soft-tissue sarcoma tumor progression, we examined the p16 gene by Southern blot analysis and PCR sequencing in 30 pairs of primary soft-tissue sarcomas and autologous normal tissue. Only one tumor sample showed possible rearrangement of the p16 gene. In contrast, Western blot analysis of the p16 protein in 20 pairs of samples showed decreased p16 expression in only 20% of the tumors but elevated p16 expression in 40% of the tumors when compared with the autologous normal controls. Overexpression of p16 was not concomitant with loss of the RB protein as is found in several other types of cancers, because more than one-half of the tumors with increased p16 expression also had high levels of RB protein. On the other hand, the p16 target protein CDK4 was overexpressed in at least 60% of the tumors. In the majority of cases, CDK4 overexpression accompanied elevated p16 and/or RB levels. Our results suggest that: (a) alteration of the p16 gene is infrequent in primary soft-tissue sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated p16 and RB levels might be the result of compensatory up-regulation of these proteins to counteract CDK4 overexpression in these tumors. Our results also suggest that it is more informative to examine aberrations in the "p16-CDK4/cyclin D-RB" pathway than to selectively examine individual components in this pathway when investigating genetic changes involved in human malignancy.
Animals↗
Locally recurrent soft tissue sarcoma of the extremities.
BACKGROUND: The management of locally recurrent extremity soft tissue sarcoma remains challenging. This study was undertaken to evaluate the long-term outcome after therapy for isolated locally recurrent soft tissue sarcoma (STS) of the extremity. METHODS: Between January 1, 1980, and December 31, 1990, 52 patients were treated at The University of Texas M. D. Anderson Cancer Center for locally recurrent extremity STS. The records of the subset of these patients (n = 36) with isolated local recurrence were examined to document clinicopathologic and treatment factors and to evaluate outcome using the end points of local recurrence-free, recurrence-free, and overall survival. RESULTS: Limb-sparing conservative surgery was possible in 24 patients (75%). Twelve (33%) of 36 patients were treated by surgery alone, 23 patients (64%) were treated with combined modality therapy (surgery plus radiation and/or chemotherapy), and 1 patient had radiotherapy only. Sixteen (44%) of 36 patients had no further recurrence of any type at a median follow-up of 58 months (range, 4 to 173 months). The 5-year actuarial local recurrence-free, recurrence-free, and overall survival rates were 72%, 45%, and 77%, respectively. CONCLUSIONS: Limb-sparing conservative surgery is possible in the majority of patients with isolated locally recurrent STS. Durable local control can be established with individualized local treatment strategies. These results support aggressive multimodality limb-sparing treatment approaches for these patients.
Adolescent↗
Telomerase activity of sarcoma cell lines and fibroblasts is independent of p53 status.
Telomerase activity is necessary for the stabilization of telomeres, which function to overcome cellular senescence and are linked to unlimited cell proliferation. Activation of telomerase is characteristic of immortalized cell lines and most tumors. The p53 gene has been implicated as a crucial barrier to unlimited cell proliferation, and its absence has been shown to allow direct immortalization of cells by certain oncogenes. The p53 gene may have an additional function of signaling cell growth arrest in response to telomere shortening, which occurs with repeated cellular divisions and ultimately threatens chromosomal stability. This prompted us to consider whether the enzyme telomerase, responsible for adding new telomeres to chromosomal ends, may be affected by the p53 status of normal and malignant cells. We investigated whether a relationship between telomerase and p53 could be demonstrated in a human sarcoma cell line containing a missense p53 mutation and several stable transfectants that express the wild-type p53 gene or a temperature-sensitive mutant of p53. All cell lines had readily detectable telomerase activity regardless of p53 status. In addition, murine fibroblast cell strains established from tissues of p53+/+ and p53-/- (p53 knockout) mice expressed telomerase regardless of the p53 status of their tissue of origin. Levels of telomerase subunit mRNA (hEST2) were comparable among cell lines and tissues with different p53 status. These results imply that p53 status is not associated with telomerase activity per se and that activation of telomerase can occur either in cells completely devoid of p53 or in cells that have functional p53.
Animals↗
Purification and characterization of human lung fibroblast motility-stimulating factor for human soft tissue sarcoma cells: identification as an NH2-terminal fragment of human fibronectin.
Paracrine motogenic factors, including motility cytokines and extracellular matrix molecules secreted by normal cells, can stimulate metastatic cell invasion. Both intact extracellular matrix molecules and their degradative products may exhibit these activities. We have found that human lung fibroblasts produce paracrine motility-stimulating factors for recently established human sarcoma cell strains. We purified the major fibroblast motility-stimulating factor (FMSF) from human lung fibroblast-conditioned medium by sequential heparin affinity chromatography and DEAE anion exchange chromatography. Lysylendopeptidase C digestion of FMSF and sequencing of peptides purified by reverse-phase high-pressure liquid chromatography identified FMSF as an NH2-terminal fragment of human fibronectin. Using SYN-1 sarcoma cells, FMSF predominantly stimulated chemotaxis and some chemokinesis, and it was chemotactic for a variety of human sarcoma cells, including fibrosarcoma, leiomyosarcoma, liposarcoma, synovial sarcoma, and neurofibrosarcoma cells. The FMSF activity present in human lung fibroblast-conditioned medium was completely eliminated by either neutralization or immunodepletion with a rabbit antihuman-fibronectin antibody, thus further confirming that the NH2-terminal fibronectin fragment was the FMSF responsible for the motility stimulation of human soft tissue sarcoma cells. Because human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), and lung-derived fibroblasts secrete large amounts of FMSF, FMSF and fibronectin may play a role in stimulating sarcoma invasion into lung tissue.
Amino Acid Sequence↗
Splenectomy in the accelerated or blastic phase of chronic myelogenous leukemia: a single-institution, 25-year experience.
BACKGROUND: Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. METHODS: We reviewed the records of 53 patients in the accelerated or blastic phases of CML who underwent splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. RESULTS: Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/microliter) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3.72-fold +/- 0.53-fold (mean +/- SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). CONCLUSIONS: Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.
Adolescent↗
Lower extremity salvage after radical resection of malignant tumors in the groin and lower abdominal wall.
BACKGROUND: Resection of a large malignant tumor in the groin often leaves a substantial soft-tissue defect that makes wound closure difficult. Nevertheless, palliation and lower extremity salvage is frequently possible if the tumor is widely excised and the wound closed with well-vascularized tissue; however, few data are available on patients undergoing such procedures. STUDY DESIGN: We retrospectively examined our experience with limb salvage in 25 patients undergoing radical groin resection for metastatic or recurrent malignant tumors between April 1, 1991 and April 8, 1996. RESULTS: Defect size ranged from 15 to 735 cm2 (mean, 238.5 cm2). Tumor resection included part of the abdominal wall in 14 patients and the femoral vessels in 5 patients. Defects were most commonly repaired with a vertical rectus abdominis myocutaneous flap (56%). Mean hospital stay was 10.4 days, and mean followup was 15.5 months. Although the complication rate was 68%, the limb salvage rate was 100%, and normal ambulation was achieved in 88% of patients. The most frequent complications were chronic lymphedema (42%) and seroma (29%). There was one perioperative death (4%). CONCLUSIONS: Functional limb salvage after radical resection of the groin and lower abdominal wall is very successful, has an acceptable morbidity rate, does not prolong hospital stay, and contributes significantly to the patient's quality of life. Chronic lymphedema is a frequent complication after this treatment but can be managed successfully with conservative techniques.
Abdominal Muscles↗
Role of splenectomy in chronic lymphocytic leukemia.
BACKGROUND: The benefit of splenectomy, performed for complications of chronic lymphocytic leukemia (CLL) including autoimmune hemolytic anemia, thrombocytopenia, hypersplenism, and symptomatic splenomegaly, has not been clearly demonstrated. The objective of this study was to determine if splenectomy achieves a predictable hematologic and survival advantage over conventional chemotherapy in patients with CLL. STUDY DESIGN: A retrospective review was performed of 77 consecutive patients with CLL who underwent splenectomy between 1970 and 1994 at the University of Texas M. D. Anderson Cancer Center. Indications for splenectomy, pre- and postoperative hematologic profiles, response to splenectomy, and time to progression and death were recorded. Kaplan-Meier life tables were constructed, and a comparison to an age- and gender-matched cohort of CLL patients treated with fludarabine and no splenectomy was performed using log rank statistical analysis. RESULTS: Seventy-six percent of the patients studied were Rai stage III/IV. Twenty of 29 patients with hemoglobin counts (Hb) < or = 10 g/dL and 11 of 18 patients with platelet counts (plt) < 50 x 10(9)/L achieved an excellent hematologic response to splenectomy. Splenectomy significantly improved survival in patients with Hb < or = 10 g/dL or plt < or = 50 x 10(9)/L (p = 0.025). Thrombocytopenia did not significantly increase postoperative morbidity, and mortality rate was not significantly different between treatment groups. CONCLUSIONS: Splenectomy significantly improves survival in selected subgroups of patients with advanced-stage CLL over that achieved with conventional chemotherapy. Based on these results, splenectomy should be performed early in the course of the disease in CLL patients with either an Hb < or = 10 g/dL or plt < or = 50 x 10(9)/L.
Antineoplastic Agents↗
Case/control study of the role of splenectomy in chronic lymphocytic leukemia.
PURPOSE: This retrospective analysis was performed to evaluate critically the morbidity and mortality of splenectomy in patients with chronic lymphocytic leukemia and to determine the probability of hematologic response. Further, using a case/control format based on multivariate analysis-derived predictors of survival, we evaluated the influence of splenectomy on survival. PATIENTS AND METHODS: Between 1971 and 1993, 55 patients with chronic lymphocytic leukemia underwent splenectomy. They were compared with 55 fludarabine-treated patients who had been matched for age, serum albumin level, sex, hemoglobin level, Rai stage, number of prior therapies, and time from diagnosis. RESULTS: In the perioperative period, blood-product usage was modest, and common morbidities were limited to minor infections in 18% of the patients and pneumonia/atelectasis in 25%. Perioperative mortality was 9%. Deaths were related to septic complications in all cases and associated with a preoperative performance status > or = 2 (P = .05). The only predictor identified for hemoglobin and neutrophil increments was spleen weight (P < .05). No factors predictive of platelet increment were identified. The early death rate (within 30 days) and overall survival of splenectomy and control patients were not significantly different (P > .2). Among Rai stage IV patients, those who were splenectomized displayed a strong trend for improved overall survival (P = .15 by log-rank test). The 2-year actuarial survival rate of Rai stage IV patients was 51% +/- 9% in the splenectomy group and 28% +/- 9% in the control group. CONCLUSION: Splenectomy can be performed with modest morbidity, mortality, and resource utilization in patients with advanced chronic lymphocytic leukemia and significant cytopenias. The procedure results in major hematologic benefits in most patients, with hemoglobin and neutrophil increments correlated with spleen weight. Overall, the survival of splenectomized patients is equivalent to control patients. Thrombocytopenic patients (< 100 x 10(9)/L) are most likely to obtain hematologic benefit, and potentially enjoy improved survival. These patients would be suitable for a randomized study to establish definitively the role of splenectomy in chronic lymphocytic leukemia.
Adult↗