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D H Leung

Publications and source records attributed to D H Leung.

At least 19 recordsLinked to original sources
PubMed2001

Clinicopathologic analysis of patients with adult rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) in adults (age > or = 16 years) is rare, accounting for less than 3% of adult soft tissue sarcomas. There is little information describing the disease biology or clinicopathologic factors that influence survival in adults with RMS. The objective of this study was to define the factors in patients with adult RMS that predict outcome, disease progression, and survival. METHODS: Eighty-four adult patients with a pathologic diagnosis of RMS that was confirmed by immunohistochemistry were identified by a prospective inpatient data base during the period 1982--1999 and were analyzed for disease specific survival and metastasis free survival using the Kaplan-Meier actuarial method. Statistical significance was evaluated using the log-rank test for univariate influence and a Cox regression model for multivariate influence. RESULTS: The median disease specific survival was 22 months. Patient age, extent of disease, tumor size at the time of diagnosis, and margin status after resection were significant predictors of disease specific survival. Patients who underwent a complete resection had a significantly longer median survival (105 months) compared with any other subgroup of patients. The histologic subtype did not predict patient survival but did vary with patient age. Most notably, the proportion of the pleomorphic subtype increased with advancing age, accounting for 42% of RMS in patients over the age of 40 years. CONCLUSIONS: The most important predictors of outcome in patients with adult RMS are patient age, tumor size, extent of disease, and margin status after resection. In contrast to patients with pediatric RMS, no association was noted between survival and histologic subtype in this group of patients with adult RMS. All histologic subtypes of RMS are aggressive malignancies with poor disease specific survival despite aggressive multimodality management.

Adolescent↗
PubMed2001

Soft tissue tumors of the abdominal wall: analysis of disease patterns and treatment.

HYPOTHESIS: Abdominal wall tumors, though clinically similar, have varying degrees of biological behavior. DESIGN: Retrospective review of prospective databases. SETTING: Memorial Sloan-Kettering Cancer Center. PATIENTS: Eighty-five patients with abdominal wall soft tissue tumors. MAIN OUTCOME MEASURES: Primary endpoints included time to first local recurrence, distant metastases, and disease-related mortality. Survival analysis was performed by Kaplan-Meier method, and comparisons were made by log-rank analysis. RESULTS: Thirty-nine desmoids, 32 soft tissue sarcomas (STS), and 14 dermatofibrosarcoma protuberans (DFSP) underwent surgery directed at achieving margin-negative resection. Unlike DFSP, most STS (77%) and desmoids(87%) were deep lesions requiring full-thickness abdominal wall resection and mesh reconstruction. Median follow-up time was 53 months, 101 months, and 31 months, with 5-year local recurrence-free survival rates of 97%, 100%, and 75%, for desmoids, DFSP, and STS, respectively. Desmoid tumors resected with positive microscopic margins had higher local failure rates (68% [positive margin] vs 100% [negative margin] 5-yr local recurrence-free survival, P<.05). For STS, high grade, deep location, and size at or above 5 cm were adverse prognostic factors for disease-specific and distant recurrence-free survival (P<.05); patients experiencing local recurrence was associated with decreased 5-year relapse-free survival rates (87% [primary] vs 50% [local recurrence], P<.05). Characteristically, no DFSP or desmoid developed distant metastases. Soft tissue sarcomas had significantly lower relapse-free survival rates than DFSP or desmoids (P<.05). CONCLUSION: Abdominal wall tumors demonstrate a broad spectrum of biological behavior. Desmoids and DFSP are a local problem. High grade, size at or above 5 cm, and deep location predict distant failure and tumor-related mortality for patients with STS. Complete surgical resection is the recommended treatment approach to achieve local control. Stratification by prognostic factors will facilitate selection of patients with STS for adjuvant systemic therapies.

Abdominal Muscles↗
PubMed2001

Validation of tissue microarrays for immunohistochemical profiling of cancer specimens using the example of human fibroblastic tumors.

Tissue microarrays allow high-throughput molecular profiling of cancer specimens by immunohistochemistry. Phenotype information of sections from arrayed biopsies on a multitissue block needs to be representative of full sections, as protein expression varies throughout the entire tumor specimen. To validate the use of tissue microarrays for immunophenotyping, we studied a group of 59 fibroblastic tumors with variable protein expression patterns by immunohistochemistry for Ki-67, p53, and the retinoblastoma protein (pRB). Data on full tissue sections were compared to the results of one, two, and three 0.6-mm core biopsies per tumor on a tissue array. Ki-67 and p53 staining was read as two categories (positive or negative). Concordance for this staining between tissue arrays with triplicate cores per tumor and full sections were 96 and 98%, respectively. For pRB staining was read as three categories (high, moderate, or negative), where concordance was 91%. The use of three cores per tumor resulted in lower numbers of lost cases and lower nonconcordance with standard full sections as compared to one or two cores per tumor. Correlations between phenotypes and clinical outcome were not significantly different between full section and array-based analysis. Triplicate 0.6-mm core biopsies sampled on tissue arrays provide a reliable system for high-throughput expression profiling by immunohistochemistry when compared to standard full sections. Triplicate cores offer a higher rate of assessable cases and a lower rate of nonconcordant readings than one or two cores. Concordance of triplicate cores is high (96 to 98%) for two category distinction and decreases with the complexity of the phenotypes being analyzed (91%).

Adolescent↗
PubMed2001

Isotonic designs for phase I trials.

The purpose of a phase I trial in cancer is to determine the level (dose) of the treatment under study that has an acceptable level of adverse effects. Although substantial progress has recently been made in this area using parametric approaches, the method that is widely used is based on treating small cohorts of patients at escalating doses until the frequency of toxicities seen at a dose exceeds a predefined tolerable toxicity rate. This method is popular because of its simplicity and freedom from parametric assumptions. In this paper, we consider cases in which it is undesirable to assume a parametric dose-toxicity relationship. We propose a simple model-free approach by modifying the method that is in common use. The approach assumes toxicity is nondecreasing with dose and fits an isotonic regression to accumulated data. At any point in a trial, the dose given is that with estimated toxicity deemed closest to the maximum tolerable toxicity. Simulations indicate that this approach performs substantially better than the commonly used method and it compares favorably with other phase I designs. Control Clin Trials 2001;22:126-138

Clinical Trials, Phase I as Topic↗
PubMed2001

Correlation of peripheral venous pressure and central venous pressure in surgical patients.

OBJECTIVE: To determine the degree of agreement between central venous pressure (CVP) and peripheral venous pressure (PVP) in surgical patients. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients without cardiac dysfunction undergoing major elective noncardiac surgery (n = 150). MEASUREMENTS AND MAIN RESULTS: Simultaneous CVP and PVP measurements were obtained at random points in mechanically ventilated patients during surgery (n = 100) and in spontaneously ventilating patients in the postanesthesia care unit (n = 50). In a subset of 10 intraoperative patients, measurements were made before and after a 2-L fluid challenge. During surgery, PVP correlated highly to CVP (r = 0.86), and the bias (mean difference between CVP and PVP) was -1.6 +/- 1.7 mmHg (mean +/- SD). In the postanesthesia care unit, PVP also correlated highly to CVP (r = 0.88), and the bias was -2.2 +/- 1.9 (mean +/- SD). When adjusted by the average bias of -2, PVP predicted the observed CVP to within +/-3 mmHg in both populations of patients with 95% probability. In patients receiving a fluid challenge, PVP and CVP increased similarly from 6 +/- 2 to 11 +/- 2 mmHg and 4 +/- 2 to 9 +/- 2 mmHg. CONCLUSION: Under the conditions of this study, PVP showed a consistent and high degree of agreement with CVP in the perioperative period in patients without significant cardiac dysfunction. PVP -2 was useful in predicting CVP over common clinical ranges of CVP. PVP is a rapid noninvasive tool to estimate volume status in surgical patients.

Aged↗
PubMed2001

Optimal designs for evaluating a series of treatments.

Several articles in this journal have studied optimal designs for testing a series of treatments to identify promising ones for further study. These designs formulate testing as an ongoing process until a promising treatment is identified. This formulation is considered to be more realistic but substantially increases the computational complexity. In this article, we show that these new designs, which control the error rates for a series of treatments, can be reformulated as conventional designs that control the error rates for each individual treatment. This reformulation leads to a more meaningful interpretation of the error rates and hence easier specification of the error rates in practice. The reformulation also allows us to use conventional designs from published tables or standard computer programs to design trials for a series of treatments. We illustrate these using a study in soft tissue sarcoma.

Biometry↗
PubMed2001

A Bayesian decision approach for sample size determination in phase II trials.

Stallard (1998, Biometrics 54, 279-294) recently used Bayesian decision theory for sample-size determination in phase II trials. His design maximizes the expected financial gains in the development of a new treatment. However, it results in a very high probability (0.65) of recommending an ineffective treatment for phase III testing. On the other hand, the expected gain using his design is more than 10 times that of a design that tightly controls the false positive error (Thall and Simon, 1994, Biometrics 50, 337-349). Stallard's design maximizes the expected gain per phase II trial, but it does not maximize the rate of gain or total gain for a fixed length of time because the rate of gain depends on the proportion of treatments forwarding to the phase III study. We suggest maximizing the rate of gain, and the resulting optimal one-stage design becomes twice as efficient as Stallard's one-stage design. Furthermore, the new design has a probability of only 0.12 of passing an ineffective treatment to phase III study.

Bayes Theorem↗
PubMed2000

Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution.

BACKGROUND: Despite optimal surgical therapy for patients with dermatofibrosarcoma protuberans (DFSP), some patients still continue to develop local recurrence. The authors' objective was to identify and analyze clinicopathologic factors for disease free survival in a large group of patients who were followed prospectively at a single institution. METHODS: Prospectively collected data and pathology slides were available for review from 159 patients with primary or recurrent DFSP who underwent treatment between July 1950 and July 1998. The study group was comprised of patients with either the "classic" form of DFSP or the fibrosarcomatous "high grade" variant of DFSP (FS-DFSP). Patient, tumor, pathologic, and treatment factors were analyzed using the log rank test for univariate influence and Cox regression analysis for multivariate influence. Local recurrence free survival was determined by the Kaplan-Meier actuarial method. RESULTS: Of the 159 patients who comprised the current study group, 134 (84%) had the classic form of DFSP. The FS-DFSP variant was found in the remaining 25 patients (16%). The overall 5-year local recurrence free survival rate was 75%, with a median follow-up of 4. 75 years. The 5-year recurrence free survival rate for each group was 81% and 28%, respectively. On univariate analysis, age > 50 years, very close (< 1 mm) to positive microscopic margins, FS-DFSP variant, high mitotic rate, and increased cellularity were unfavorable prognostic factors. Multivariate analysis determined very close (< 1 mm) to positive microscopic margins and FS-DFSP variant to be independent adverse prognostic factors. For the 34 patients who developed a recurrence after surgical resection (21%), the median time to local recurrence was 32 months. Of the patients in this group, two died from metastatic disease. CONCLUSIONS: The prognosis after surgical resection with negative and sometimes positive microscopic margins for patients with DFSP is very good. However, increased age, high mitotic index, and increased cellularity are predictors of poor clinical outcome. The FS-DFSP variant represents a much more aggressive tumor with metastatic potential. Patients who are treated with curative intent for FS-DFSP should undergo aggressive attempts at complete surgical resection. Patients with recurrent classic DFSP without evidence of adverse prognostic features may benefit from conservative management, especially in the setting of potentially unresectable disease.

Adolescent↗
PubMed2000

Alterations of cell cycle regulators in localized synovial sarcoma: A multifactorial study with prognostic implications.

Genetic alterations of cell cycle regulators are thought to represent uncommon and possible secondary events in sarcomas characterized by recurrent chromosomal translocations. The present study investigates this hypothesis on synovial sarcoma (SS), assessing the frequency of expression and possible clinical implications of detecting alterations in critical cell cycle regulatory proteins. A homogeneous cohort of 49 patients with localized SS, restricted to the extremity and with available long-term follow-up information, was selected from our files. We focused our study on molecules involved in the G1 checkpoint and G1-S transition, including cyclins D1 and E, p21(WAF1), p27(Kip1), mdm2, p53, and Ki67. A cutoff point of 10% immunoreactive tumor cell nuclei was selected to define a positive phenotype for any given marker, except for Ki67. High Ki67 proliferative index was considered when >/=20% tumor cells displayed nuclear immunoreactivity. Biphasic SS were analyzed, taking into account separately the expression of these proteins in the spindle and glandular components. Disease specific survival was modeled using the Kaplan-Meier method with log rank test and Cox regression. The cohort of patients analyzed included 23 females and 26 males, and the histological type distribution was 35 monophasic and 14 biphasic SS. The median follow-up for survivors was 53 months, with a 5-year disease-specific survival of 63% and a metastatic disease-free survival of 40%. The positive phenotypes identified for the different markers studied were as follows: cyclin D1, 59%; cyclin E, 29%; p21, 51%; p27, 69%; mdm2, 59%; p53, 16%; and Ki67, 59%. We observed that positive p53, cyclin E, and high Ki67 proliferative index were correlated with survival, but only Ki67 and p53 were independent variables for prognostication. The present study suggests that alterations of cell cycle regulators are more common events in SS than originally thought. p53 overexpression could be of use as a marker together with a high Ki67 proliferative index, in identifying a subset of SS patients with increased risk of tumor relapse.

Adolescent↗
PubMed2000

Perioperative alterations in plasma endothelin-1 and echocardiographic correlates of right heart function.

OBJECTIVE: To determine whether greater changes in plasma endothelin-1 (ET-1) concentrations and right ventricular systolic pressure occur after major thoracic surgery than after major abdominal operations. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective thoracotomies (n = 12) or laparotomies (n = 10). INTERVENTIONS: ET-1 was measured from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). Transthoracic echocardiography was performed before surgery and on postoperative day 2 to evaluate right-sided heart function. MEASUREMENTS AND MAIN RESULTS: After abdominal and thoracic surgery, systemic and estimated pulmonary vascular pressures were normal in both groups and unaffected by surgery. Plasma ET-1 concentrations decreased from baseline values during the first postoperative week with no differences between the groups. CONCLUSIONS: In patients without organic heart disease, plasma ET-1 levels do not increase in response to major abdominal or thoracic surgery. Whether or not plasma ET-1 concentrations are elevated in patients developing clinically significant postoperative pulmonary hypertension requires further study.

Aged↗
PubMed2000

Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma.

BACKGROUND: Even after an apparent complete resection of sarcomatous pulmonary metastases, 40% to 80% of patients will re-recur in the lung. The benefit of subsequent re-resection is poorly defined. This study examines patient survival after repeat pulmonary exploration for re-recurrent metastatic sarcoma at a single institution. STUDY DESIGN: Between July 1982 and December 1997, data on 3,149 adult in-patients with soft tissue sarcoma were prospectively gathered. Of these, pulmonary metastases were present or developed in 719 patients and 248 underwent at least one resection. Of the patients relapsing in the lung after an apparently complete resection, 86 underwent reexploration. Disease-specific survival (DSS) after re-resection was the end point of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event end points was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. Clinicopathologic factors were analyzed with the Pearson chi-square or Fisher's exact test when appropriate. RESULTS: The median DSS after re-resection for all patients undergoing at least two pulmonary resections was 42.8 months with an estimated 5-year survival of 36%. The median DSS in patients with complete reresection was 51 months (n = 68) compared with 6 months in patients with an incomplete re-resection (n = 16, p<0.0001). Patients with one or two nodules at re-resection (n = 39) had a median DSS of 51 months compared with 20 months in patients with three or more nodules (n = 40, p = 0.003). Patients in whom the largest metastasis re-resected was less than or equal to 2 cm (n = 33) had a median DSS of 44 months compared with 20 months in patients with metastasis greater than 2 cm (n = 43, p = 0.033). Patients with primary tumor high-grade histology (n = 75) had a median DSS of 32 months and patients with low-grade histology (n = 11) had a median DSS that was not reached (p = 0.041). Three independent prognostic factors associated with poor outcomes may be determined preoperatively: > or =3 nodules, largest metastases > 2 cm, and high-grade primary tumor histology. Patients with either zero or one poor prognostic factor had a median DSS > 65 months and patients with three poor prognostic factors had a median DSS of 10 months. CONCLUSIONS: Reexploration for recurrent sarcomatous pulmonary metastases appears beneficial for patients who can be completely re-resected. Outcomes are described by factors that may be determined preoperatively, including metastasis size, metastasis number, and primary tumor histologic grade. Patients who cannot be completely re-resected or those with numerous, large metastasis and high-grade primary tumor pathology have poor outcomes and should be considered for investigational therapy.

Adolescent↗
PubMed2000

Surgical management of intra-abdominal desmoid tumours.

BACKGROUND: Intra-abdominal desmoids are uncommon neoplasms. The aggressive nature of these tumours and the potential for major morbidity secondary to resection can present a difficult surgical dilemma. METHODS: Patients with histologically confirmed intra-abdominal desmoid tumours undergoing laparotomy were identified from a prospective database. Clinical features and outcomes in this group were evaluated. RESULTS: The study group comprised 24 patients. Sixteen patients underwent complete resection of the tumour while eight had biopsy only, with or without intestinal bypass. Small intestinal resection was performed in 12 patients, including three who had a near-total enterectomy. Median follow-up was 62 months, with an actuarial overall survival rate of 73 per cent at 10 years. There was no difference in survival rate between completely resected and unresected patients (P = 0.73). There were seven deaths in the entire group, of which four were in those undergoing complete resection. CONCLUSION: Operation can cure patients with intra-abdominal desmoid tumours, but may result in significant morbidity, especially from loss of small intestine. No other therapy is a predictably good alternative to operation but the natural history of desmoids is often characterized by prolonged periods of stability or even regression. A period of watchful waiting, until significant symptoms develop, may be the most appropriate course in patients who risk mesenteric vascular injury or substantial enterectomy with attempts at resection.

Abdominal Neoplasms↗
PubMed2000

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.

UNLABELLED: Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. BACKGROUND: In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. METHODS: After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). RESULTS: In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). CONCLUSION: In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Aged↗
PubMed2000

Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery.

OBJECTIVES: We sought to determine whether early prophylaxis with an L -type calcium channel blocker reduces the incidence and morbidity associated with atrial fibrillation/flutter and supraventricular tachyarrhythmia after major thoracic operations. METHODS: In this randomized, double-blind, placebo-controlled study, 330 patients were given either intravenous diltiazem (n = 167) or placebo (n = 163) immediately after lobectomy (> or =60 years) or pneumonectomy (> or =18 years) and orally thereafter for 14 days. The primary end point with respect to efficacy was a sustained (> or =15 minutes) or clinically significant atrial arrhythmia during treatment. RESULTS: Postoperative atrial arrhythmias (atrial fibrillation/flutter = 60; supraventricular tachyarrhythmias = 5) occurred in 25 (15%) of the 167 patients in the diltiazem group and 40 (25%) of the 163 patients in the placebo group (P = .03). When compared with placebo, diltiazem nearly halved the incidence of clinically significant arrhythmias (17/167 [10%] vs. 31/163 [19%], P = .02). The 2 groups did not differ in the incidence of other major postoperative complications or overall duration or costs of hospitalization. No serious adverse effects caused by diltiazem were seen. CONCLUSIONS: After major thoracic operations, prophylactic diltiazem reduced the incidence of clinically significant atrial arrhythmias in patients considered at high risk for this complication.

Administration, Oral↗
PubMed2000

Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma.

Synovial sarcoma is characterized by a specific recurrent translocation t(X; 18), resulting in either the SYT-SSX1 or SYT-SSX2 gene fusion. Because this is the primary genetic alteration in these tumors, we sought to identify the impact of molecular heterogeneity of the t(X;18) on cell proliferation, apoptosis, and epithelial differentiation in synovial sarcoma. Seventy-three patients with synovial sarcoma (18 biphasic, 55 monophasic) were selected on the basis of availability of tumor material for molecular and immunohistochemical analysis. Tumors were classified as biphasic on the basis of morphologic glandular differentiation. SYT-SSX fusion transcripts were examined by reverse transcriptase polymerase chain reaction using tumor RNA extracted from frozen or paraffin-embedded tissue. Cell proliferation was assessed immunohistochemically by the Ki-67 labeling index. Apoptosis was analyzed immunohistochemically with BAX and BCL2 antibodies and by the TUNEL method. Immunohistochemical evidence of epithelial differentiation was assessed using antibodies to cytokeratins and epithelial membrane antigen. Approximately two thirds of the tumors had an SYT-SSX1 and one third had an SYT-SSX2 fusion transcript. There was a strong association between SYT-SSX fusion type and histologic subtype. All biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology. There was, however, no association between SYT-SSX fusion type and expression of cytokeratins and epithelial membrane antigen among monophasic tumors. Tumors with SYT-SSX2 had a significantly higher mean and median Ki-67 labeling index than those with SYT-SSX1, but a comparison of Ki-67 according to fusion type, histologic type, and sample source suggested that the main determinants of proliferation rate were the latter two factors. Specifically, monophasic tumors and metastatic tumors showed significantly higher Ki-67 scores. Apoptosis (by TUNEL) was rarely observed, consistent with prominent expression of the anti-apoptotic protein BCL2 in almost all cases. TUNEL, BCL2, and BAX results did not correlate with SYT-SSX fusion type. These data confirm the strong association of SYT-SSX fusion transcript type with morphologic but not immunophenotypic epithelial differentiation in synovial sarcoma.

Apoptosis↗
PubMed2000

Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity.

PURPOSE: Synovial sarcoma is a high-grade tumor that is associated with poor prognosis. Previous studies analyzing prognostic factors are limited because of inclusion of heterogeneous cohorts of patients with nonextremity and recurrent tumors. The objective of this study was to determine independent prognostic factors of primary synovial sarcoma localized to the extremity. PATIENTS AND METHODS: Between July 1, 1982, and June 30, 1996, 112 patients underwent surgical resection for cure at our institution and then were followed-up prospectively. Clinical and pathologic factors examined for prognostic value included age, sex, tumor site and location, depth, size, microscopic status of surgical margins, invasion of bone or neurovascular structures, and monophasic or biphasic histology. The end points analyzed were the time to first local recurrence that was not preceded by a distant recurrence, time to any distant recurrence, and time to disease-related mortality. These end points were modeled using the method of Kaplan and Meier and analyzed by the log-rank test and Cox regression. RESULTS: The median duration of follow-up among survivors in this cohort of 112 patients was 72 months. The 5-year local-recurrence, distant-recurrence, and mortality rates were 12%, 39%, and 25%, respectively. Tumor size > or = 5 cm (P =.001; relative risk [RR] = 2. 7; 95% confidence interval [CI], 1.5 to 5.2) and the presence of bone or neurovascular invasion (P =.04; RR = 2.3; 95% CI, 1.0 to 5. 3) were independent adverse predictors of distant recurrence. Tumor size > or= 5 cm (P =.003; RR = 2.3; 95% CI, 1.4 to 6.3) and the presence of bone or neurovascular invasion (P =.03; RR = 2.7; 95% CI, 1.0 to 6.5) were also independent adverse predictors of mortality. CONCLUSION: The natural history of primary synovial sarcoma of the extremity is related to tumor size and invasion of bone and neurovascular structures.

Adolescent↗
PubMed1999

Extremity and trunk desmoid tumors: a multifactorial analysis of outcome.

BACKGROUND: The natural history of desmoid tumors remains an enigma. Previous reports attempting to identify their biology have included recurrent and primary tumors as well as tumors from both intra- and extra-abdominal sites. The purpose of this study was to analyze patients with primary extremity and trunk desmoid tumors treated and followed at a single institution and to determine factors influencing disease free survival. METHODS: Between July 1982 and June 1997, 189 patients with extremity and superficial trunk desmoid tumors were treated and followed prospectively. Of these, 105 presented with primary disease and formed the basis of this study. RESULTS: The median follow-up for the entire group of patients was 49 months; it was 46 months for patients who did not develop a local recurrence. During this time, 24 patients (23%) had a local recurrence. No patients died of disease. The 2-year and 5-year local recurrence free survival rates were 80% and 75%, respectively. None of the prognostic factors analyzed, including age, gender, depth of tumor, size of tumor, or tumor site, were significant for predicting local recurrence. Moreover, positive resection margins were not predictive of recurrence. The selective use of adjuvant radiation therapy did not influence the rate of local recurrence regardless of the margin status. CONCLUSIONS: Attempts to achieve negative resection margins may result in unnecessary morbidity and may not prevent local recurrence. Operations that preserve function and structure should be the primary goal, because the presence of residual disease cannot be clearly shown to impact adversely on 5-year disease free or overall survival.

Adult↗