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Marshall M Urist

Publications and source records attributed to Marshall M Urist.

13 recordsLinked to original sources

Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPSs) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates. Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue expander to limit exposure of small bowel to higher radiation doses. METHODS: Between June 1999 and December 2003, 16 consecutive patients with biopsy-proven RPS were treated with preoperative radiation with selective dose escalation. This included 45 grays (Gy) in 25 fractions to the entire tumor plus margin and a boost dose of 57.5 Gy to the volume predicted as high risk for positive surgical margins. Treatment toxicity and local control were evaluated prospectively as primary endpoints. The secondary goal was the theoretical calculation of future dose escalation and feasibility. Each patient underwent laparotomy. Tumor response was judged using computed tomography (CT) scan and by necrosis on final pathology. Theoretical treatment plans evaluated the potential for additional radiation dose escalation. RESULTS: All patients completed the radiation protocol. The most common acute side effects were nausea/vomiting, which affected 4 patients (25%), with only 1 patient requiring inpatient intravenous hydration. There was no severe late postoperative morbidity or mortality. Twelve tumors (75%) decreased in maximum dimension, with a median decrease of 9.4%. Fourteen of 16 patients (88%) underwent complete macroscopic resection. With a median follow-up of 28 months (range, 7-52 months), there were only 2 local recurrences. The actuarial 2-year local control rate was 80%. Theoretical treatment plans suggest that significant dose escalation (up to 80 Gy) may be possible. CONCLUSIONS: Preoperative radiation therapy with selective dose escalation to the margin at risk is tolerable and allows higher radiation dose to the volume judged to be at greatest risk for local tumor recurrence.

Adult↗

Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma.

PURPOSE: To evaluate the prognostic significance of molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR) in detecting occult melanoma cells in sentinel lymph nodes (SLNs) and circulating bloodstream. PATIENTS AND METHODS: In this multicenter study, eligibility criteria included patient age 18 to 71 years, invasive melanoma > or = 1.0 mm Breslow thickness, and no clinical evidence of metastasis. SLN biopsy and wide excision of the primary tumor were performed. SLNs were examined by serial-section histopathology and S-100 immunohistochemistry. A portion of each SLN was frozen for RT-PCR. In addition, RT-PCR was performed on peripheral-blood mononuclear cells (PBMCs). RT-PCR analysis was performed using four markers: tyrosinase, MART1, MAGE3, and GP-100. Disease-free survival (DFS), distant-DFS (DDFS), and overall survival (OS) were analyzed. RESULTS: A total of 1,446 patients with histologically negative SLNs underwent RT-PCR analysis. At a median follow-up of 30 months, there was no difference in DFS, DDFS, or OS between the RT-PCR-positive (n = 620) and RT-PCR-negative (n = 826) patients. Analysis of PBMC from 820 patients revealed significant differences in DFS and DDFS, but not OS, for patients with detection of more than one RT-PCR marker in peripheral blood. CONCLUSION: In this large, prospective, multi-institutional study, RT-PCR analysis on SLNs and PBMCs provides no additional prognostic information beyond standard histopathologic analysis of SLNs. Detection of more than one marker in PBMC is associated with a worse prognosis. RT-PCR remains investigational and should not be used to direct adjuvant therapy at this time.

Adult↗

Gender-related differences in outcome for melanoma patients.

OBJECTIVE: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma. SUMMARY BACKGROUND DATA: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood. METHODS: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). CONCLUSIONS: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Adolescent↗

Melanoma.

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Algorithms↗

E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7.

Studies suggest the expression of cyclooxygenase-2 (COX-2) and matrilysin (MMP-7) increase in the early stages of colorectal carcinogenesis, however their interaction with other molecular markers is poorly understood. Results from cell line studies and mouse models suggest polyomavirus enhancer activator 3 (PEA3) may play a role in the activation of COX-2 and MMP-7 promoters. However, the role of E1A-F, the human homolog of murine PEA3, in colorectal cancer (CRC) development has not been elucidated. In this study, we used real-time reverse transcription (RT)-polymerase chain reaction (PCR) to measure the levels of E1A-F, COX-2, and MMP-7 in matched normal mucosa, adenomas, and/or carcinomas from 128 patients. Our results demonstrate significant overexpression of E1A-F and MMP-7 in adenomas and E1A-F, COX-2, and MMP-7 in carcinomas. In carcinomas, E1A-F expression was significantly associated with both COX-2 and MMP-7 overexpression. These results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7.

Adenovirus E1A Proteins↗

Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer.

OBJECTIVE: To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. SUMMARY BACKGROUND DATA: The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. METHODS: Effect of celecoxib in cell culture: The effect of 40 micromol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean +/- SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80 degrees C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. RESULTS: Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase in 15-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 +/- 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 +/- 0.4 and 5.0 +/- 0.1 cm, respectively. Expression of 15-LOX-1 relative to S9 was 30 in normal mucosa and significantly down-regulated to 11 in adenomas and 16 in carcinomas (P < 0.05). CONCLUSIONS: 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and associated with decreased survival. Administration of celecoxib restores 15-LOX-1 protein expression and induces apoptosis. Down-regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence, and reversal with celecoxib may represent one mechanism for chemoprevention of polyps or treatment of carcinomas.

Adenoma↗

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: an interim analysis of a prospective multi-institutional cohort study.

OBJECTIVE: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. BACKGROUND: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established. METHODS: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. RESULTS: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. CONCLUSION: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

Adult↗

Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer.

OBJECTIVE: To assess the significance of axillary lymph node status and tumor size for predicting locoregional recurrence (LRR) and overall survival after mastectomy for breast cancer and to discuss the utility of postmastectomy radiation therapy. SUMMARY BACKGROUND DATA: Patients with locally advanced breast cancer require multimodality treatment combining chemotherapy (and/or hormonal therapy), surgery, and radiation. Randomized trials have demonstrated that postmastectomy radiation reduces LRR, but no overall survival benefit has been established. METHODS: Criteria for accrual to the Alabama Breast Cancer Project (1975-1978) were female gender and T2-3 breast cancer with M0 status. Patients underwent a radical or a modified radical mastectomy. Node-positive patients received adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy or adjuvant melphalan. Patients were evaluated for LRR and overall survival based on the number of positive axillary lymph nodes and (in N0 patients) pathologic tumor size. Significance was determined using chi-square analysis. Survival curves were generated using the Kaplan-Meier method and were compared by log-rank analysis. RESULTS: After median follow-up of 15 years, neither type of surgery nor chemotherapy was shown to affect locoregional disease-free or overall survival. LRR rates were higher and overall survival rates were lower in patients with nodal involvement, while tumor size was not shown to significantly affect these rates. CONCLUSIONS: Patients with axillary lymph node metastases may benefit from postmastectomy radiation, but the use of postmastectomy radiation in N0 patients is not supported when it is based on tumor size alone.

Adult↗

Laparoscopic adrenalectomy and splenectomy are safe and reduce hospital stay and charges.

The proposed benefits of laparoscopy for certain surgical procedures have been decreased post-operative pain and hospital stay balanced against the proposed deficits of increased costs. We have reviewed our data to evaluate factors associated with patient, procedure, and hospital charges for patients undergoing open versus laparoscopic adrenalectomy and splenectomy during the same time period. Eighty-seven patients underwent adrenalectomy (n = 47) or splenectomy (n = 40) from October 30, 1995 to June 6, 2001 and were retrospectively reviewed. Patient and operative factors were analyzed by intent to treat; the major endpoints were operating room (OR) time in minutes, blood loss in cm3, length of hospital stay in days, and charges broken down by anesthesia/operation [OR/recovery room (RR)] and total charges in dollars x 1000. Comparisons of means were analyzed by unpaired t test; data are presented as mean +/- SEM, and significance is defined as P < 0.05. Median age of the group was 47 years (range 20-77). Forty-five patients underwent a laparoscopic approach of which two were converted to open (4%) as compared with 42 undergoing an open operation; one patient from each group was excluded from outcome analyses because of prolonged hospitalization (>3 weeks). Operative mortality of the whole group was one per cent. There were no differences between the groups with respect to age, gender, or comorbidity. The laparoscopic group had significantly longer operative times and OR/RR charges. However, the length of hospital stay and the total charges for the patient undergoing a laparoscopic approach were significantly less (P < 0.05). We conclude that a laparoscopic approach for adrenalectomy or splenectomy can be accomplished in approximately 95 per cent of patients selected for this procedure. Despite prolonged OR time and increased OR/RR charges the laparoscopic procedures resulted in significantly decreased length of hospital stay and overall patient charges. Laparoscopy is a safe and cost-effective approach and should be strongly considered in patients requiring adrenalectomy or splenectomy.

Adrenalectomy↗

Results of long-term follow-up for transanal excision for rectal cancer.

Low anterior resection and abdominoperineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. It is our hypothesis that selected patients with early T stage, well or moderate grade of differentiation, and small tumor size are good candidates for transanal excision in terms of minimal morbidity, low recurrence rate, and sphincter preservation. From January 1993 until August 2001 30 patients underwent transanal excision; three patients were excluded because they had histology other than adenocarcinoma. Factors analyzed included those related to the patient [age (years), gender, race, body mass index, and anal tone], tumor [size (cm), distance from the anal verge (cm), differentiation, and American Joint Committee on Cancer stage], and additional treatment. Median follow-up of the group was 40.7 months (range 0.6-99) and the primary end points were local and distant recurrence. Data are presented as mean (range). The median age of the group was 58.9 years (range 27-94); 52 per cent were female and 48 per cent were male. The mean body mass index was 25.9 (range 22.7-36.7). Preoperatively 81, 11, and 4 per cent of the patients had stage I, II, and III/IV cancer, respectively. Preoperative size of the tumor was 2.0 cm (1-3 cm), and distance from the anal verge was 5.0 cm (3-15 cm). Blood loss was 50 cm3 (5-200 cm3), and there were no operative complications. Tumor differentiation levels were well (37%) and moderate (63%). All patients had negative margins. Additional treatment consisted of radiation therapy in seven patients (six postoperative and one preoperative). Chemotherapy was given to seven patients (six postoperative and one preoperative). The local recurrence rate was 7.4 per cent (two patients), and 3.7 per cent recurred distantly (one patient). Transanal excision of low rectal cancer in selected patients is an acceptable alternative to formal resection. Important selection criteria include early T stage, well or moderate differentiation, relatively small tumor size, and negative microscopic margins. The roles of radiation and chemotherapy remain controversial.

Adenocarcinoma↗

Factors associated with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer.

OBJECTIVE: To examine the incidence of local recurrence (LR) and factors associated with it in a population of patients who underwent skin-sparing mastectomy (SSM) and immediate reconstruction for invasive carcinoma. SUMMARY BACKGROUND DATA: The efficacy of SSM has been challenged by concerns about increased risks of LR. METHODS: A consecutive series of 173 patients (176 cancers) with invasive carcinoma underwent SSM and immediate breast reconstruction (June 1986 to December 1997). Data were analyzed by the Kaplan-Meier method, the log-rank statistic test, and the Cox proportional hazards model. RESULTS: Mean patient age was 47 +/- 9 years (27% were 40 or younger). The AJCC stages were 1 = 43%, 2 = 52%, and 3 = 5%. Thirty percent of tumors were poorly differentiated. With a median follow-up of 73 months, the LR rate was 4.5%. The mean local relapse-free interval was 26 months. Seventy-five percent of patients who presented with LR developed distant metastases and died of disease within a mean of 21 months. On univariate analysis, factors associated with higher LR rate were tumor stage 2 or 3, tumor size larger than 2 cm, node-positive disease, and poor tumor differentiation. Actuarial 1-, 3-, and 5-year overall survival rates were 98%, 94%, and 88%, respectively. On multivariate analysis, factors associated with decreased survival were advanced stage, presence of LR, and absence of hormone therapy. LR was a highly significant predictor of tumor-related death. CONCLUSIONS: There is a low incidence of LR after SSM, and it is associated with advanced disease at presentation. LR is an independent risk factor for tumor-related death.

Adult↗

Occult breast carcinoma presenting with axillary lymph node metastases.

BACKGROUND AND OBJECTIVES: Occult primary breast carcinoma is uncommon. Most reported series encompass a large periods of time with great variability in diagnostic and treatment approaches. The objective of the present study was to review the recent experience with this type of presentation of breast cancer in the University of Alabama at Birmingham. METHODS: Retrospective review of clinicopathological data of female patients presenting with axillary metastasis of adenocarcinoma with unknown primary and normal clinical and mammographic breast exam seen at UAB between 1985 and 1998. RESULTS: Ten patients were identified. Mean age was 56 years. Sixty per cent were white and postmenopausal. All patients had biopsy proven adenocarcinoma consistent with breast primary. All but one patient underwent an axillary dissection. Nine out of ten patients received some type of local treatment to the breast. Three of them underwent mastectomy and no invasive carcinoma was demonstrated in the surgical specimens. Six patients received radiation therapy to the breast. All patients received chemotherapy. With mean follow-up time of 48 months, two patients developed local recurrence to the axilla and four developed distant metastasis and eventually died. At last follow-up six patients are alive with no evidence of disease. CONCLUSIONS: In presence of axillary metastasis from an unknown breast primary, an extensive work-up evaluation is not necessary. An axillary dissection is recommended to provide prognostic indicators as well as local control. A breast conservation approach seems to be feasible without affect the local control and survival.

Adenocarcinoma↗