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Mario M Leitao

Publications and source records attributed to Mario M Leitao.

13 recordsLinked to original sources
PubMed2006

Surgical resection of recurrent endometrial carcinoma.

OBJECTIVE: Chances of survival after the diagnosis of recurrent endometrial cancer are poor. Although total pelvic exenteration has been described as a treatment for a select subset of patients with recurrent endometrial cancer, the use of other surgical procedures in this setting has not been well described. The objective of this study was to review our experience with non-exenterative surgery for recurrent endometrial cancer. METHODS: We reviewed the medical records of all patients who underwent non-exenterative surgery for recurrent endometrial cancer between 1/91 and 1/03. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. RESULTS: Twenty-seven patients were identified. Fifteen patients (56%) had disease limited to the retroperitoneum, 10 patients (37%) had intraperitoneal disease, and 2 patients (7%) had both intra- and retroperitoneal disease. Cytoreduction to 2 cm. There were no major perioperative complications or mortalities. The median hospital stay was 7 days (range, 1-18 days). Additional therapies included intraoperative radiation therapy in 9 patients (33%), radiation therapy in 12 patients (44%), and chemotherapy in 10 patients (37%). The median follow-up for the entire cohort was 24 months (range, 5-84 months). The median progression-free survival was 14 months (95% CI, 6-23), and the median disease-specific survival was 35 months (95% CI, 24-not reached). Size of residual disease was the only significant predictor for both progression-free and disease-specific survival. Patients with residual disease 2 cm residual (P = 0.01). CONCLUSIONS: Surgical resection for recurrent endometrial cancer may provide an opportunity for long-term survival in a select patient population. The only factor associated with improved long-term outcome was the size of residual disease remaining at the end of surgical resection.

Aged↗
PubMed2005

Expression of cancer-testis antigens in endometrial carcinomas using a tissue microarray.

Cancer-testis (CT) antigens are expressed in a variety of malignant tumors, but in normal adult tissue, they are only expressed in testicular germ cells. Owing to this tumor-associated expression pattern, these antigens are of major interest as potential targets for immunotherapy and possibly for diagnostic purposes. This study was performed to analyze the expression of four CT antigens, NY-ESO-1, MAGE-A3, MAGE-A4, and CT7/MAGE-C1, in endometrial carcinoma using immunohistochemistry, and to correlate expression with histologic subtypes, grade, and expression of WT1 and p53. Formalin-fixed paraffin-embedded tissues of 130 endometrial carcinomas of the following types and grades were analyzed using a tissue microarray: 85 endometrioid carcinomas (FIGO grade 1, 39; grade 2, 11; and grade 3, 35), 18 papillary serous carcinomas, 12 clear cell carcinomas, 13 malignant mixed mullerian tumors, one mucinous adenocarcinoma, and one undifferentiated carcinoma. The following anti-CT monoclonal antibodies/antigens were studied by immunohistochemistry: monoclonal antibody ES121/NY-ESO-1, monoclonal antibody M3H67/MAGE-A3, monoclonal antibody 57B/MAGE-A4, and monoclonal antibody CT7-33/CT7. The CT expression data were compared to WT1 and p53 protein expression as analyzed in a previous study. Positive staining with anti-CT monoclonal antibodies was graded as follows: focal, <5% positive cells; 1+, 5-25% cells; 2+, 26-50% cells; 3+, 51-75%; and 4+, >75% cells. The 3+ and 4+ staining patterns were considered homogeneous patterns of potential clinical significance and were scored positive for statistical analysis. In low-grade tumors, the most immunoreactivity was seen with mAb M3H67 but little labeling was observed with the other monoclonal antibodies. In high-grade tumors, monoclonal antibodies M3H67 (25%), 57B (23%), and CT7-33 (20%) showed the highest reactivity, while ES121 showed the lowest immunoreactivity (6%). The staining pattern was mostly heterogeneous. Statistical significance was found solely for the correlation of monoclonal antibody 57B staining and p53 expression. No correlation was found for any anti-CT monoclonal antibody staining and clinical stage or for anti-CT staining and WT1 expression. CT antigens CT7, MAGE-A3 and MAGE-A4, but not NY-ESO-1, are expressed in high-grade endometrial carcinomas, and expression of MAGE-A4 is correlated with the presence of overexpressed p53.

Adenocarcinoma, Clear Cell↗
PubMed2005

Invasion patterns in stage I endometrioid and mucinous ovarian carcinomas: a clinicopathologic analysis emphasizing favorable outcomes in carcinomas without destructive stromal invasion and the occasional malignant course of carcinomas with limited destructive stromal invasion.

Stage I, low-grade endometrioid and mucinous ovarian carcinomas have an excellent prognosis. Published data have suggested that destructive stromal invasion, a relatively uncommon finding in these tumors, is a poor prognostic factor. We investigated this by studying all FIGO stage I, grades 1 and 2 (of 3) endometrioid and mucinous ovarian carcinomas that were surgically staged at the Memorial Sloan-Kettering Cancer Center from 1980 to 2000. We undertook a careful review of all available slides using current diagnostic criteria and correlated histopathologic indices with clinical outcome data. Cases studied included 13 endometrioid ovarian carcinomas (stage IA, eight; stage IC, five) and six intestinal mucinous ovarian carcinomas (stage IA, three; stage IC, three). All of the tumors contained areas of expansile invasion, greater than that acceptable for microinvasion, and were thus diagnosed as carcinomas instead of borderline tumors. Nevertheless, nearly all demonstrated borderline tumor (noninvasive) components. Six tumors contained at least one focus of destructive stromal invasion (two endometrioid and four mucinous ovarian carcinomas). Four additional cases showed a focus suspicious for but not diagnostic of destructive invasion ('indeterminate for destructive invasion') (two endometrioid and two mucinous ovarian carcinomas). Follow-up data were available for 17 patients. The median follow-up was 81 months (range, 9-161 months). In all, 14 patients were alive with no evidence of disease (expansile invasion alone, eight; destructive stromal invasion, four; and indeterminate for destructive invasion, two). Three patients died of their disease (destructive stromal invasion, two; and indeterminate for destructive invasion, one). The size, number, and nuclear grade of destructive stromal invasion foci did not appear to have an impact on survival in this relatively limited number of patients. Outcome data in patients with stage I, low-grade endometrioid and mucinous ovarian carcinomas without destructive stromal invasion indicate that these tumors have a very limited malignant potential. The literature has not documented recurrences in this setting when the staging has been complete, the sampling adequate, and the cytologic features no more than grade 2, and metastasis to the ovary has been excluded. In contrast, carcinomas harboring even limited foci of destructive stromal invasion, although frequently cured surgically, can pursue a malignant clinical course.

Adenocarcinoma, Mucinous↗
PubMed2005

Fertility-sparing options for patients with gynecologic malignancies.

Gynecologic malignancies are most often diagnosed in postmenopausal women, but these malignancies also arise in premenopausal women, in whom issues of fertility can be a major concern. An increasing number of women are delaying childbearing. This has led to a significant increase in the number of women diagnosed with a gynecologic malignancy before desired completion of childbearing. Many of the standard treatments for these malignancies result in permanent sterility; however, there are now options for select young women who desire to preserve fertility. Patients should be told that data on fertility-sparing procedures are limited and that many of these options are of an experimental, nonstandard nature. The care of these patients is challenging and complex and requires a multidisciplinary approach, which should include gynecologic oncologists, reproductive endocrinologists, and perinatologists.

Endometrial Neoplasms↗
PubMed2004

Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma.

BACKGROUND: Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS. METHODS: Between January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0-1) and positive (2-3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determined from the time of the initial diagnosis to last follow-up. RESULTS: ER, PR, and AR positivity in LMA compared with LMS was as follows: ER, 78% versus 40% (P = 0.03); PR, 88% versus 38% (P = 0.001); and AR, 32% versus 40% (P = 0.75). There was no difference noted with regard to IHC expression based on stage of LMS. The median overall survival for patients with LMS was 23.5 months (95% confidence interval, 19.5, NR). When adjusted for stage, PR and AR were found to be predictive of a lower risk of recurrence (P = 0.01 and P = 0.035, respectively). ER, PR, and AR were not found to be associated with overall survival after adjustment for stage. Tumor stage was found to be associated with survival (P = 0.005). CONCLUSIONS: The rate of ER and PR expression was found to be significantly less in uterine LMS compared with LMA. ER, PR, and AR expression was observed in approximately 30-40% of uterine LMS cases. In the current series, PR and AR expression appeared to be associated with disease-free survival but were not found to correlate with overall survival.

Adult↗
PubMed2004

Mutation and expression of the TP53 gene in early stage epithelial ovarian carcinoma.

OBJECTIVE: The early natural history of epithelial ovarian carcinoma remains poorly understood. Mutation of the TP53 gene is common in advanced-stage (III-IV) ovarian cancers, but less well described in early stage (I-II) tumors. The purpose of this study was to perform a comprehensive analysis of TP53 mutation and p53 expression status in early stage ovarian carcinomas. METHODS: Seventy-three cases of various histologic types, including 46 stage I and 27 stage II tumors, were subjected to direct sequence analysis of the entire TP53 coding region and exon-intron junctions as well as immunohistochemical assessment of p53 expression. RESULTS: Overall, mutations were identified in 24 of 73 (34%) cases. However, a significant difference in the distribution of mutations among histologic types was observed; TP53 mutations were present in 14 of 21 (67%) serous cancers and 11 of 52 (21%) non-serous cancers (P = 0.0002). Mutations were equally common between stage I and stage II tumors of serous histology. With respect to the correlation between TP53 mutation and p53 immunopositivity, the sensitivity (58%), specificity (71%), positive predictive value (64%), and negative predictive value (83%) were not sufficiently robust to justify use of p53 expression as a surrogate or screen for mutation. CONCLUSIONS: These data indicate that TP53 mutation is common in early stage ovarian carcinomas of serous histology, with a mutation frequency comparable to that reported for advanced-stage tumors, and is therefore likely to occur early in the progression of the most common histologic variant of ovarian carcinoma.

Epithelial Cells↗
PubMed2004

Tertiary cytoreduction in patients with recurrent ovarian carcinoma.

OBJECTIVES: The literature on the role of cytoreductive surgery beyond the secondary cytoreductive setting is limited. In this study, we reviewed the outcomes of patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction. METHODS: We performed a retrospective chart review of all patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction at our institution from 1/1/90 to 12/31/02. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors. RESULTS: A total of 26 patients were identified. The median follow-up after tertiary cytoreduction was 22.3 months (range, 0-71.7 months), with an overall median DSS of 33.4 months (95%CI, 20.4-46.4). On univariate analysis, treatment-free interval (TFI) before tertiary cytoreduction and residual disease after the procedure, as well as time to first recurrence, were found to be significant prognostic factors. Median DSS was 15 months for a TFI < or =12 months compared with 60.4 months for a TFI > 12 months (P = 0.002). The median DSS for patients with residual disease < or =0.5 cm was 36.3 months compared with 10.6 months for patients with residual disease >0.5 cm (P <0.0001). On multivariate analysis, TFI and residual disease after tertiary cytoreduction retained prognostic significance (P < 0.05 for both). CONCLUSION: Further cytoreductive surgery may offer a survival benefit in patients who experience a recurrence after secondary cytoreduction. This benefit appears to be greatest in patients with a longer TFI (>12 months) and in whom an optimal (< or = 0.5 cm) cytoreduction can be achieved.

Adult↗
PubMed2004

Clinicopathologic analysis of early-stage sporadic ovarian carcinoma.

The reported experience with early-stage (FIGO stage I/II) ovarian carcinoma (OC) is limited given that the majority of women with OC are diagnosed at an advanced stage. There has not been an extensive review of these tumors, and since the pathologic criteria differentiating invasive and borderline tumors have evolved over time, the issue of whether a proportion of these tumors should be reclassified has not been addressed. We identified patients with stage I/II invasive OC who underwent primary surgical management at Memorial Sloan-Kettering Cancer Center from 1980 to 2000. Patients known to have a BRCA mutation or a family history of breast/ovarian cancer were excluded. Hematoxylin and eosin slide review, blinded to clinical outcomes, using current diagnostic criteria for ovarian carcinomas and borderline ovarian tumors, was performed. Progression-free survival (PFS) and disease-specific survival (DSS) were estimated and compared. Hematoxylin and eosin slides were reviewed for 140 of the 145 patients identified. The diagnosis was changed to borderline (low malignant potential) in 41 cases (29.3%). Twenty-nine (70.7%) of 41 changes in diagnosis involved endometrioid and mucinous tumors. This was attributable to the application of recently revised criteria for distinguishing borderline tumors from carcinomas. None of the originally diagnosed clear cell carcinomas was reclassified as borderline. The distribution of histologic subtypes among the 94 carcinomas included 26 serous (27.7%), 25 clear cell (26.6%), 22 endometrioid (23.4%), 10 mixed (10.6%), 6 mucinous (6.4%), 2 malignant Brenner (2.1%), and 3 adenocarcinomas, not otherwise specified (3.2%). Adjuvant therapy was given to 84 (89.4%) of the 94 patients with carcinomas. The 5-year PFS and DSS were significantly greater for the group of cases that was reclassified as borderline (4.5% vs. 26.2% progressed [P = 0.006]; 4.5% vs. 25.6% died [P = 0.003]). The 5-year PFS and DSS were significantly worse for carcinomas with a TP53 mutation (22.6% vs. 41.2% progressed [P = 0.04]; 21.7% vs. 24.7% died [P = 0.04]). There were no statistically significant differences in outcome between stages I versus II, tumor grades, clear cell histology versus other, and stage IC preoperative versus intraoperative rupture. We concluded that a large number of cases originally diagnosed as early-stage sporadic OC were borderline tumors. Clear cell histology does not confer a worse prognosis compared with other histologies. The presence of a TP53 mutation was an adverse prognostic indicator.

Adult↗
PubMed2003

Platinum retreatment of platinum-resistant ovarian cancer after nonplatinum therapy.

OBJECTIVE: The objective was to determine the response rate to platinum retreatment of "platinum-resistant" ovarian cancer after intervening nonplatinum therapy. METHODS: We retrospectively identified 30 patients with platinum-resistant ovarian cancer who received nonplatinum chemotherapy for recurrent epithelial ovarian cancer prior to additional platinum therapy. All patients were treated between July 1, 1997, and June 30, 2001. Platinum resistance was defined as less than a partial response to platinum therapy or progression within 6 months of the last platinum therapy. RESULTS: Overall, 7 of 30 patients experienced an objective response to platinum therapy (partial response, 23%; complete response, 0%) based on CT scan (2/21) and/or CA-125 (5/9) criteria. The median time to progression for the group was 17 weeks (range, 4-59 weeks). Several predictive factors were identified. The interval since the last platinum treatment did not appear to be predictive in this group. Only 1 of 16 patients who did not have an objective response to the most recent platinum-based therapy responded to platinum rechallenge. Similarly, no patient who received more than three intervening nonplatinum treatments responded to additional platinum therapy (0/10). CONCLUSIONS: Our small retrospective series suggest that the platinum-resistant category is heterogenous and includes patients who may respond to retreatment with platinum-based agents. This group includes the patients with prior platinum responses and early progression. However, patients without an objective response to the last prior platinum therapy or more than three intervening treatments are unlikely to respond to subsequent platinum therapy.

Adult↗
PubMed2003

Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus.

OBJECTIVE: The purpose of this study was to determine the incidence of lymph node and ovarian metastases in newly diagnosed uterine leiomyosarcoma (LMS), and to describe possible predictive factors. METHODS: We used our prospectively acquired databases to identify 275 consecutive patients with uterine LMS treated from 7/82 to 12/01. Patients were included if there was clear documentation of lymph nodes and/or ovarian tissue in the pathologic reports. Clinical data were extracted from electronic medical records. Statistical analysis using the Fisher exact test was used to determine prognostic factors. RESULTS: There were 108 patients (39.2%) identified in whom an oophorectomy and 37 patients (13.5%) in whom lymph node sampling was performed as part of the initial surgical management of uterine LMS. Bilateral oophorectomy was performed in 102 (94.4%) of the 108 patients. The median numbers of pelvic, para-aortic, and total lymph nodes acquired were 5 (range, 1-27), 3 (range, 1-9), and 6 (range, 1-34), respectively. Ovarian metastases were found in 4 (3.9%) out of 108 patients. Two (2.8%) of the 71 patients with disease confined to the uterus and/or cervix (stage I/II) and 2 (5.4%) of the 37 patients with gross extrauterine disease had ovarian metastases (P = 0.43). Positive lymph nodes were seen in 3 (8.1%) of 37 patients. No patients with stage I/II disease had positive lymph nodes (P = 0.015). None of the factors analyzed predicted for metastases to the ovary. Only the presence or absence of gross extrauterine disease correlated with lymph node metastasis. In addition, all three of these cases had clinically suspicious (enlarged) lymph nodes. CONCLUSIONS: The incidence of ovarian and lymph node metastases in uterine LMS is very low and is most commonly associated with extrauterine disease. Lymph node dissection for uterine LMS should be reserved for patients with clinically suspicious nodes.

Adult↗
PubMed2002

Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma.

OBJECTIVE: The objective was to determine long-term survival and predictors of outcome in a retrospective cohort of patients who underwent surgical resection of recurrent uterine leiomyosarcoma (LMS). METHODS: Between January 1991 and March 2001, 41 patients who underwent surgical resection for recurrent uterine leiomyosarcoma were identified. The records of these patients were reviewed and abstracted data included patient age, date of initial diagnosis, tumor histology and grade, residual tumor after all operations, the use of adjuvant therapy, dates and sites of all recurrences, and disease status at last follow-up. Survival was determined from the time of first recurrence to last follow-up. Survival curves were estimated using the Kaplan-Meier method and P values were generated using the likelihood ratio test from the Cox proportional hazards model and chi(2) analysis. RESULTS: Forty-one patients with recurrent uterine LMS (17 local pelvic, 18 distant, 6 both) underwent surgical resection at time of first recurrence. A thoracic procedure alone was performed in 13 cases. Information on residual disease was available for 37 patients. The disease-specific 2-year survival for all 41 patients was 71.2% (95% CI: 58.1, 87.3). In univariate analysis, time to first recurrence and optimal resection were significantly associated with longer overall survival. CONCLUSION: Optimal surgical resection for recurrent uterine leiomyosarcoma may provide an opportunity for long-term survival in a select patient population. Time to first recurrence and optimal surgical resection were predictors of improved outcome in this study.

Adult↗
PubMed2002

Recurrent cervical cancer.

There are limited treatment options for patients with recurrent cervical carcinoma. Because of low response rates and a negligible impact on long-term survival, the use of chemotherapy in patients with unresectable recurrent disease should be considered palliative. Generally, radiation therapy in previously irradiated patients is considered palliative. For patients who develop recurrent disease after definitive surgery who have not received prior radiation therapy, salvage radiation therapy is the treatment of choice. Similarly, patients who have received definitive primary radiation therapy are candidates for surgical resection of their recurrence. However, there are specific criteria for surgical resection. Radical hysterectomy may be an option for the very rare patient with a small (<2 cm) centrally located recurrence in the cervix or vaginal fornices. However, for most patients, pelvic exenteration remains the only therapeutic option that offers the possibility of long-term survival. Patients who are candidates for exenteration are those with central local recurrences that have not extended to the pelvic sidewalls. The introduction of high-dose-rate intraoperative radiation therapy (HDR-IORT) combined with radical surgical resection has widened the scope of patients who may be offered surgery. Patients who in the past may not have been surgical candidates may benefit from radical surgical resection combined with HDR-IORT. All patients who are surgically fit and have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. Patients whose recurrences extend close to the pelvic sidewalls should be referred to centers where HDR-IORT is available.

Brachytherapy↗