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Biomedical subjects

R E Pollock

Publications and source records attributed to R E Pollock.

At least 73 records · Page 4Linked to original sources

Immediate versus delayed free-tissue transfer salvage of the lower extremity in soft tissue sarcoma patients.

BACKGROUND: Free tissue transfer (FTT) can extend the limits of limb salvage in patients with soft tissue sarcoma (STS), but few data exist on the efficacy and morbidity in this patient population. METHODS: We prospectively examined 19 patients who underwent resection of STS and an immediate or a delayed FTT reconstruction between November 1989 and May 1992. RESULTS: There were 11 immediate and eight delayed FTT reconstructions (mean age 52 years). All delayed patients presented with complications resulting from previous STS treatment. Defects involved the leg (n = 7), knee (n = 2), and thigh (n = 10) and had a mean size of 129 cm2, 154 cm2, and 283 cm2, respectively. Preoperative radiatiotherapy had been administered to 74% of patients in the series (mean dose 53 Gy). FTT success rate was 95% (one failure in the delayed group). Limb salvage and postreconstruction ambulatory rates were both 95%. The overall complication rate was 47%, with the trend of a higher rate (63%) in the delayed group compared with the immediate group (36%). The immediate reconstruction group required no additional operative procedures before FTT and had a shorter hospital stay (13 days) compared with that of the delayed reconstruction group (40.6 days). Mean follow-up was 11.9 months (range 2-30). CONCLUSIONS: FTT is a reliable and versatile adjunctive treatment for lower extremity salvage of patients with STS. Immediate reconstruction appears to carry a lower complication rate and a faster rehabilitation for the patient.

Female↗

Comparison of charges related to radiotherapy for soft-tissue sarcomas treated by preoperative external-beam irradiation versus interstitial implantation.

BACKGROUND: We compared treatment-related charges associated with external beam irradiation and interstitial implantation for soft-tissue sarcoma of the extremity. METHODS: Charges related to radiotherapy in 35 patients with soft-tissue sarcoma of the extremity were reviewed. Preoperative external beam irradiation (EB) delivering 50 Gy in 25 fractions with 6 MV photons was administered to 12 of the patients evaluated. The remaining 23 patients were treated with interstitial implantation (IR) as the only radiotherapeutic intervention. The anatomic distribution of the sarcomas treated by IR included 14 lower-extremity (LE) and nine upper-extremity (UE) lesions. The average length of iridium wire used for IR was 78 cm. Because LE lesions tend to be larger, the average length equaled 109.5 cm as compared with the 47 cm for UE implants. RESULTS: The radiotherapeutic approach represented the only difference in treatment-related charges because the operative procedure of wide local excision was performed in each group. No difference in perioperative complications was observed between the two treatment approaches. Charges were stratified according to hospital-based and professional services. Radiotherapy-based hospital charges for the administration of EB averaged $6,515 compared with $4,050 for IR (p < 0.0001). Professional services also were significantly different, totaling $4,390 for EB and $3,240 for IR (p < 0.0001). The total of these charges for radiotherapy procedures and professional fees equaled $10,905 for EB compared with $7,290 for IR (p < 0.0001). Incorporating the necessary operating-room time for implant placement ($750) and five additional hospital days ($1,800), the costs associated with IR totaled $9,840; using chi-square analysis, the cost for IR remained significantly (p < 0.0001) less expensive than the $10,905 associated with EB. Because a large component of the radiotherapy cost for IR is related to the length of iridium 192 wire required, charges were stratified according to the location of the tumor. The total charge for IR of the UE equaled $9,345 compared with $10,335 for LE implants. Chi-square comparison for both UE and LE implants continued to show significant differences (p < 0.0001) when related to EB therapy. CONCLUSION: Cost-analysis comparison of brachytherapy versus external beam irradiation found lower charges for patients undergoing adjuvant irradiation with brachytherapy for soft-tissue sarcoma. To optimize the cost-benefit ratio, prospective studies are necessary to define the application of these radiotherapeutic approaches based on clinical criteria.

Arm↗

Risk of dissemination of cancer to flap donor sites during immediate reconstructive surgery.

We reviewed a series of 617 immediate reconstructions with distant flaps of defects caused by extirpation of malignant tumors to determine the incidence of tumor implantation in the flap donor sites. In this large series, there was only one instance of tumor dissemination to a flap donor site. We conclude that, despite possible theoretical concerns about host immunosuppression caused by surgical stress, the risk of tumor dissemination to flap donor sites as a consequence of immediate reconstruction is negligible.

Humans↗

Limb-sparing therapy for soft tissue sarcomas.

Effective therapy for soft tissue sarcoma of the extremities continues in its lengthy evolution from mandatory amputation or radical compartment resection to multimodality limb salvage procedures. This current approach typically includes preoperative neoadjuvant systemic chemotherapy, followed by negative margin surgical resection in conjunction with radiotherapy. The scope and functional outcome of these resections has been markedly enhanced by the application of microvascular-dependent free tissue transfer techniques. Because of the rarity of this tumor system, problems in soft tissue sarcoma receive proportionally less attention. Nonetheless, the past year has witnessed several important advances in this field, as is discussed.

Amputation, Surgical↗

Sarcoma of the breast: implications for extent of therapy. The M. D. Anderson experience.

BACKGROUND: Sarcoma of the breast is a rare clinical entity for which there are no prospective data about extent of surgery indicated or role of multimodality therapy. The purpose of this study was to examine one of the largest single institutional experiences to shed light on these clinical issues. METHODS: This study retrospectively reviewed 60 cases of sarcoma of the breast (cystosarcoma phyllodes excluded). RESULTS: For the entire series there was a median overall survival time (OS) of 67 months and a disease-free survival period (DFS) of 18 months. Tumors smaller than 5 cm were associated with a better DFS (p < 0.04) and OS (p < 0.009). Patients with tumors less than 5 cm in diameter did equally well whether treated by wide local excision or mastectomy. Angiosarcoma histologic characteristics were associated with longer OS than stromal sarcoma (p = 0.017), malignant fibrous histiocytoma (p = 0.075), or fibrosarcoma (p = 0.08). Axillary dissections did not recover any nodal metastasis; moreover, treatment in 75% of the patients with negative nodes subsequently failed. Regional lymph node metastases were always and only in the context of disseminated disease. Adjuvant chemotherapy and/or radiotherapy was associated with prolonged DFS (p = 0.015). There was a trend toward improved local control with adjuvant radiotherapy (p = 0.14). CONCLUSIONS: Lesions less than 5 cm should be treated by breast-preserving wide local excision, and adjuvant radiotherapy should be considered for selected subgroups. For tumors 5 cm or larger, a more aggressive approach seems appropriate; consideration should be given to neoadjuvant chemoradiation followed by margin-negative surgery (if possible). There is no demonstrable staging or therapeutic role for routine axillary dissection.

Adolescent↗

Durable hepatic tumor regression after arterial chemoembolization-infusion in patients with islet cell carcinoma of the pancreas metastatic to the liver.

BACKGROUND: Islet cell carcinoma of the pancreas is a neuroendocrine tumor often presenting with left upper quadrant mass and radiographic evidence of liver metastases. Because survival among these patients is determined largely by the pace of metastatic events in the liver, significant palliation may be achieved by regional hepatic therapy. METHODS: Five patients with islet cell carcinoma of the pancreas metastatic to the liver (four nonfunctional, one gastrin producing), were treated by hepatic arterial chemoembolization-infusion consisting of a mixture of polyvinyl alcohol sponge (150 mg) and cisplatin (150 mg) followed by 2-hour intraarterial infusion of vinblastine (10 mg/m2). Each patient received two such treatments, 1 month apart, requiring 3 to 6 days of hospital admission. RESULTS: Significant tumor regression (> 50%) was observed in four of five patients, lasting from 8 to 44 months. Toxicity was limited to right upper quadrant pain, paralytic ileus requiring nasogastric suction for 24 to 72 hours, transient, mild bilirubinemia and liver enzyme elevation, hypomagnesemia and hypokalemia, and occasionally, moderate, self-limiting granulocytopenia. CONCLUSIONS: This preliminary, albeit limited, experience with hepatic chemoembolization-infusion in patients with islet cell carcinoma metastatic to the liver emphasizes the high incidences of durable tumor regression that can be achieved with minimal iatrogenic intervention.

Adenoma, Islet Cell↗

Effect of surgery on peripheral blood lymphocyte locomotion through type I collagen.

BACKGROUND: Locomotion of peripheral blood lymphocytes (PBL) through peritumoral matrix is obligatory for tumor cell killing. The authors investigated the effect of surgery on lymphocyte locomotion and compared it with the effect on natural killer cell cytotoxicity (NKCC). METHODS: PBL from 12 patients with cancer were assessed for locomotion in Type I rat-tail collagen. Preoperative and postoperative locomotion (after 20 hours of incubation) and NKCC were estimated. RESULTS: Locomotion of lymphocytes through collagen increased significantly after operation in 6 of 12 patients, whereas only 1 of 12 had a decrease (P < 0.001). Short-term (20-hour incubation) exposure of the locomotory HSB cell line to patient plasma samples did not affect their migration. NKCC, as estimated against K562 target cells with the use of the 51Cr-release assay, decreased 5-50% after operation in 9 of 12 patients (P = 0.006). No correlation could be demonstrated between the changes in locomotion and NKCC (regression analyses), nor were identifiable clinical factors associated with these changes. CONCLUSIONS: Locomotion of PBL through collagen increases after operation in patients with cancer, whereas possibly independent factors may decrease postoperative NKCC.

Cell Movement↗

Isolated splenic metastases from colon carcinoma.

It is generally accepted that splenic metastases from colorectal carcinoma occur concurrently with widespread dissemination of the tumor. The case reviewed is notable for its long disease-free interval, isolated splenic metastasis and favorable-outcome postsplenectomy. It represents the fourth case report in the English literature of surgical resection for an isolated splenic metastasis from colorectal carcinoma.

Adenocarcinoma↗

Surgical stress impairs natural killer cell programming of tumor for lysis in patients with sarcomas and other solid tumors.

BACKGROUND: Natural killer (NK) cells may provide a first line of defense against the metastatic implantation of circulating tumor emboli. Because tumor emboli are discharged systemically in patients undergoing solid tumor resection, it is important to determine the nature of surgical-stress impairment of perioperative NK cell cytotoxic function. METHODS: The authors studied 85 patients undergoing surgical resection of solid tumors, most of whom had an abrupt and marked decrease in NK cell cytotoxicity that was detectable within 18 hours of surgical resection. RESULTS: This impairment was not caused by rapidly emerging suppressor cells (measured in autologous effector cell mixing studies) or decreased NK cell frequency in the peripheral blood (assessed phenotypically and morphologically). Instead, surgical stress exerted a direct "toxic" effect on NK cells that could be localized to a specific phase of the NK cell tumor lysis cycle. Tumor binding and the first round of tumor lysis were intact postoperatively (measured in single-cell assays). However, postbinding programming for lysis was decreased sharply after surgery (assessed by calcium pulse assays). In addition, the kinetics of lysis and the rate of lytic programming were slower after surgery (assayed in target saturation kinetic chromium-51 release tests). CONCLUSIONS: These latter defects probably were related to the programming for lysis deficiency because postprogramming NK cell maximal recycling capacity was not affected by surgical stress.

Cell Separation↗

Prognostic factors in 227 patients with malignant fibrous histiocytoma.

Malignant fibrous histiocytoma, the major subset of soft tissue sarcomas, was examined for prognostic factors that could influence clinical management and research. Two hundred twenty-seven patients with localized disease, having surgery as the principal modality, were reviewed retrospectively to identify clinical outcomes. The mean age of the patients was 54 years. Extremities were the primary tumor site in 157 patients (62.2%). Overall survival rate was 50%, including 38 patients who died of other causes. Distant metastases were most common to the lung (90%). Local recurrence alone occurred in 37 patients (16%), distant metastases alone in 52 (23%), and distant metastases with local recurrence in 25 (11%). The primary tumor size indicated the 5-year survival rate: tumors smaller than 5 cm had a survival rate of 82%; 5 to 10 cm, 68%; and larger than 10 cm, 51%. Intermediate-grade tumors yielded a 5-year survival rate of 80%, and the 5-year survival rate for high-grade tumors was 60%. Survival rates for both grades were affected by size: tumors of high grade and smaller than 5 cm in diameter had a survival rate of 79%; 5 to 10 cm, 63%; and more than 10 cm, 41%. Grade and size emerge as significant prognostic indicators. These variables will prove helpful in treatment decisions and design of clinical studies.

Adolescent↗

Prognostic implications of patterns of failure for gastrointestinal leiomyosarcomas.

One hundred ninety-one patients with gastrointestinal leiomyosarcomas were analyzed to determine the prevalence in patterns of failure and the factors predicting those at higher risk of relapse at specific sites. Of 100 assessable patients who died of disease, 89% were found to have peritoneal tumor, 78% had liver metastases, and 32% had extraabdominal metastases. Of 132 patients (69%) with initial complete resection of the primary tumor, only 10% (n = 13) remained free of disease as of the last follow-up. The median interval to recurrence was 18 months; 60% of all recurrences occurred within 2 years after surgery. Half of these patients (n = 61) had metastases (predominantly in the liver) as the initial recurrence. Factors significantly associated with improved survival after relapse were initial disease-free interval of 18 months or more, recurrences either isolated to the peritoneal cavity or within the liver, or complete resection of peritoneal recurrences or liver metastases. In contrast, those patients with recurrences at multiple sites or unresectable disease had significantly shorter survival times. The presence of extraabdominal metastases also heralded an equally poor outcome. In conclusion, a multimodality approach is necessary to improve outcome from this disease because the liver and peritoneal cavity represent predominant sites of failure. Complete resection of isolated peritoneal or hepatic metastases improves survival and should be attempted when feasible.

Adolescent↗

Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging.

The appropriate surgical therapeutic options for either localized or more advanced disease in patients with gastrointestinal leiomyosarcomas remain unclear. A staging classification for this disease has not been adopted nor risk factors identifying patients at risk for recurrence defined. To address these issues, this study evaluated the influence of various clinicopathologic variables on overall and disease-free survival. In an univariate analysis of overall survival involving 191 patients, the Cox proportional hazards model identified four factors that were associated with a significantly better outcome: complete resection without tumor rupture (p less than 0.001), localized lesions (p less than 0.001), low grade of tumor (p = 0.02), and tumors smaller than 5 cm (p = 0.03). When interactive effects of these factors were taken into account, however, type of resection of the tumor was selected as the only significant prognostic factor in a multivariate analysis. Complete resection without tumor rupture improved overall survival of patients with localized disease (median, 46 months) as well as those with contiguous organ invasion (median, 36 months) or peritoneal implants (median, 36 months). In contrast, patients with incomplete resections survived for a median of 21 months. Patients with tumor rupture, despite removal of all gross disease, behaved similarly to those with incomplete resections; median survival was only 17 months. For disease-free survival, important determinants selected from a multivariate analysis were tumor rupture (p = 0.002), contiguous organ invasion (p = 0.02) and high tumor grade (p = 0.02). A staging classification incorporating these prognostic factors of significance was evaluated using a TGM system: T1 (less than 5 cm), T2 (greater than or equal to 5 cm), T3 (contiguous organ invasion or peritoneal implants), T4 (tumor rupture); G: G1 (low grade), G2 (high grade); M: M0 (no metastases), M1 (metastases present). The corresponding 5-year overall survivals for stages I, II, III, IVA, and IVB were 75%, 52%, 28%, 12%, and 7%. Disease-free survival at 2 years after surgery was 89%, 57%, and 47% for stages I, II, and III, respectively. In conclusion, surgery remains the primary modality of treatment for patients with gastrointestinal leiomyosarcomas, and complete resection of all disease without tumor rupture, even of locally advanced disease, improves overall and disease-free survival. A staging classification appears feasible and is recommended to determine outcome in patients with leiomyosarcomas arising from the gastrointestinal tract.

Actuarial Analysis↗

Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity.

Natural killer (NK) cells are an important defense against intravascular tumor dissemination. Tumor embolization can occur at surgery, so we tested whether surgical stress decreased perioperative NK cell cytotoxicity, and examined the underlying mechanism of suppression. Patients with solid tumors underwent NK cell cytotoxicity assay just before and 24 hours after surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was significantly decreased postoperatively. We considered that surgical NK cell impairment might be due to (1) NK cell redistribution, (2) presence of suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK cell cytotoxicity was not due to NK cell redistribution, because differential counts showed no significant changes in the percentage of large granular lymphocyte NK morphology. To isolate possible suppressor cells, postoperative cells from patients were selectively depleted of NK cells using anti-Leu-11b monoclonal antibody plus complement; these cells were then mixed with autologous preoperative cells. Postoperative NK cell cytotoxicity was markedly impaired, but the postoperative NK depleted cells did not suppress preoperative NK cells. We conclude that NK cell functional impairment from surgical stress is due to direct "toxic" effects on NK cells rather than either NK cell redistribution or the generation of NK-directed suppressor cells.

Antibodies, Monoclonal↗

Extremity epithelioid sarcoma. Amputation vs local resection.

Amputation has traditionally been advised for extremity epithelioid sarcoma because of its pattern of innocuous presentation and relentless soft-tissue and nodal metastasis. To assess the role of amputation in extremity epithelioid sarcoma, we reviewed our experience with 42 patients treated between 1961 and 1986. On presentation with localized primary tumor (n = 18), nine of 11 patients who underwent wide local excision and four of six patients who underwent excisional biopsy were free of disease, and one patient who underwent amputation died. After presentation with localized recurrence (n = 12), four of six patients who underwent wide local excision and two patients who underwent excisional biopsy were free of disease; three other patients who underwent wide local excision had margins that tested positive on pathologic examination, of whom one was free of disease; one patient who underwent amputation died of disease. On presentation with regional metastasis (n = 12), only one of five patients who underwent wide local excision and one of seven patients who underwent amputation were free of disease. Primary amputation offered no apparent overall survival benefit to patients presenting with regional metastasis. The favorable outcome after local resections for localized disease indicates that wide local excision with margins that test negative on pathologic examination is preferable to radical amputation in these patients.

Adult↗

Antitumor activity, growth, and phenotype of long-term IL-2 cultures of human NK and T lymphocytes.

We have studied growth, function, and phenotype of purified NK and T cells in long-term cultures and compared these parameters to those of conventionally prepared interleukin-2-activated lymphocytes with killer cell activity (LAK). Enrichment of NK and T cells was achieved by Percoll density gradient. Growth was analyzed by cell counts and [3H]TdR uptake. Cytotoxicity and tumor-binding efficacy were assessed in a 3-h 51Cr and single cell agarose assay, respectively, against K-562, Daudi, human ovarian cell line Ovcar-3, and fresh leukemic blasts. We found that long-term proliferation and lytic activity were highest in NK-enriched and lowest in T-enriched cultures. Conventional LAK cultures generated medium cytotoxicity levels. Lytic activity declined within 3 weeks in cultures not enriched for NK cells, while NK-enriched cultures showed high levels of cytotoxicity up to 6 weeks. No change was found in binding activity within 3 weeks with the exception of T cell-enriched fraction. A number of changes in the phenotypic patterns was observed in IL-2 cultures; the CD56+/CD3-/+ and CD56+/CD8+ subset increased in most cultures, whereas the CD56-/CD3+ subset decreased over time. The highly enriched NK cell culture maintained its NK cell phenotype over 5-6 weeks. We also delineated the most cytotoxic lymphocyte subset in long-term IL-2 cultures by complement dependent cytotoxic assays and fluorescence-activated cell sorting (FACS). Lytic activity in conventional LAK as well as in T and NK cell-enriched IL-2 cultures was mediated primarily by CD56+, CD16+, CD3- NK cells. The clinical implication of these studies is discussed.

Cell Division↗

Human Kupffer cells are cytotoxic against human colon adenocarcinoma.

Colorectal liver metastases are a common clinical problem and require more effective therapy. Kupffer cells (KC) perform many important homeostatic functions within the liver and may also possess the ability to mediate tumor cytotoxicity. We investigated the ability of human KC to mediate cytotoxicity against human colon adenocarcinoma targets (HT 29) in vitro. Unstimulated human KC were cytotoxic against the HT 29 targets at all effector/target ratios tested. This cytotoxicity was increased significantly (p less than 0.05) when the KC were stimulated with interferon-gamma and lipopolysaccharide. Human KC produced tumor necrosis factor (TNF), and KC stimulation significantly (p less than 0.05) increased secretion of this monokine. The addition of anti-TNF antibody to the KC-HT 29 cocultures completely neutralized all of the available TNF yet cytotoxicity was not affected, suggesting the participation of a membrane-bound form of TNF or other mechanisms.

Adenocarcinoma↗

Lytic units reconsidered: pitfalls in calculation and usage.

51Chromium release-derived cytotoxicity data yield curvilinear plots when the x axis displays the effector:target ratio and the y axis displays the percentage of cytotoxicity. To facilitate data analysis, several biomathematical models (simple linear regression, exponential fit, and Von Krogh) have been used to express these cytotoxicity curves as a single numerical value, termed the lytic unit. Other than using raw cytotoxicity data, the lytic unit has been the most common method of data presentation in human and animal tumor immune studies involving natural killer cells, lymphokine-activated killer cells, and cytotoxic T cells. Unfortunately, the models for determining lytic unit values incorporate assumptions and methods of calculation that can result in inaccurate model-predicted cytotoxicity in comparison with the actual observed cytotoxicity data. Even when the model is accurate in predicting cytotoxicity values (i.e., the nonlinear regression-calculated three-parameter Von Krogh model), comparisons between donors of minimally different or highly different cytotoxicity are still fraught with potential error due to statistically verifiable violations of assumptions of parallelism. Although more cumbersome, donor cytotoxicity comparisons using a range of effector:target ratios are not subject to the above problems. Researchers may therefore want to reconsider the use of lytic units when evaluating and reporting cytotoxicity data.

Chromium Radioisotopes↗