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Biomedical subjects

Pedro F Escobar

Publications and source records attributed to Pedro F Escobar.

18 recordsLinked to original sources
PubMed2006

The 2003 revised TNM staging system for breast cancer: results of stage re-classification on survival and future comparisons among stage groups.

BACKGROUND: Changes to TNM staging criteria for breast cancer, introduced in 2003, have resulted in stage re-classification for some tumors. The most frequently implemented change has resulted in tumors associated with more than three positive axillary nodes being upstaged. We hypothesize these TNM staging changes would result in more TNM Stage IIB, IIIA, and IIIB tumors and that disease-specific survival estimates would change under the new staging system. METHODS: A review of data was completed for patients diagnosed with breast cancer between 1 January 1995 and 31 December 2000. Tumors that would have been staged differently under the 2003 system were identified and re-classified. Clinical outcomes were determined and disease-specific survival estimates were compared relative to TNM Stage using the old and new staging systems. Data were analyzed using the log-rank test and the method of Kaplan and Meier was used to generate survival curves. RESULTS: Data were available for 2492 tumors, of which 919 were candidates for re-classification, including 829 old Stage II, 59 old Stage III, and 31 old Stage IV. Of these 919, 159 (17%) underwent stage re-classification using the new system. Separate survival estimates for patients who had been under old stage IIA/B, IIIA/B were generated; patients upstaged from IIA or IIB demonstrated a significant difference in survival. CONCLUSIONS: Stage specific survival curves indicated decreased survival for patients whose tumors had been upstaged from IIA or IIB under the old system; survival for all other patients remained unchanged.

Adult↗
PubMed2006

Hypoxia enhances lysophosphatidic acid responsiveness in ovarian cancer cells and lysophosphatidic acid induces ovarian tumor metastasis in vivo.

Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and stimulates growth and other activities of ovarian cancer cells in vitro. Tissue hypoxia is a critical factor for tumor aggressiveness and metastasis in cancers. We tested whether the ascites of ovarian cancer is hypoxic and whether hypoxia influences the effects of LPA on ovarian cancer cells. We found that ovarian ascitic fluids were hypoxic in vivo. Enhanced cellular responsiveness to LPA, including migration and/or invasion of ovarian cancer cells, was observed under hypoxic conditions. This enhancement could be completely blocked by geldanamycin or a small interfering RNA targeting hypoxia-inducible factor 1 alpha (HIF1 alpha). LPA-induced cell migration required cytosolic phospholipase A(2) (cPLA(2)) and LPA stimulates cPLA(2) phosphorylation in a HIF1 alpha-dependent manner under hypoxia conditions. Furthermore, we show for the first time that exogenous LPA enhances tumor metastasis in an orthotopic ovarian cancer model and HIF alpha expression in tumors. 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (an inhibitor of the heat shock protein 90) effectively blocked LPA-induced tumor metastasis in vivo. Together, our data indicate that hypoxic conditions are likely to be pathologically important for ovarian cancer development. HIF1 alpha plays a critical role in enhancing and/or sensitizing the role of LPA on cell migration and invasion under hypoxic conditions, where cPLA(2) is required for LPA-induced cell migration.

Cell Hypoxia↗
PubMed2006

A data model to predict HER2 status in breast cancer based on the clinical and pathologic profiles of a large patient population at a single institution.

Recently published clinical trial data have produced compelling evidence for increased survival when Herceptin is administered to patients whose tumors are HER2 amplified. Therefore, the accuracy of HER2 status is essential to determine which patients should or should not receive Herceptin. Although HER2 results obtained by FISH and IHC are often in agreement, there is a persistent group of cases in which results are discordant, particularly among tumors with intermediate results. A multivariable analysis was undertaken to determine relative significance of various clinical and pathologic findings for patients diagnosed with infiltrating ductal carcinoma, and a data model was produced that predicts which patients are most likely to have HER2 amplified tumors. Correlates of HER2 amplification were higher Scarff-Bloom-Richardson grade, younger age at diagnosis, and a comedo ductal carcinoma in situ component.

Adult↗
PubMed2006

Prognostic significance of residual breast disease and axillary node involvement for patients who had primary induction chemotherapy for advanced breast cancer.

BACKGROUND: We performed this study to determine the prognostic significance of clinical tumor size, pathologic measurement of residual tumor, and number of positive axillary nodes in the surgical specimen relative to overall survival for patients who underwent primary induction chemotherapy for advanced breast cancer. METHODS: Data, collected prospectively between 1997 and 2002, included clinical tumor-node-metastasis stage, age at diagnosis, hormone receptor status, type of preoperative chemotherapy, histological type, surgical procedure, pathologic measurement in centimeters of residual breast tumor, and the number of positive axillary nodes in the surgical specimen. Univariable correlates of residual breast disease were assessed by using the chi2 test. Recursive partitioning analysis was used to determine the prognostic significance of clinical tumor size, residual tumor size, and pathologic node involvement relative to overall survival. Survival was estimated by using the method of Kaplan and Meier and compared by using the log-rank test. A P value of <.05 was considered significant. RESULTS: Data were available for 85 patients with advanced breast cancer. Although univariable analysis identified increasing age, clinically involved axillary nodes, and a higher clinical tumor-node-metastasis stage as predictors of an increased risk of residual disease, recursive partitioning analysis identified more than three involved axillary nodes in the surgical specimen, with or without any measurable residual breast disease, as the most significant predictor of decreased survival (P<.001). CONCLUSIONS: Pathologic axillary node involvement was the most significant predictor of decreased survival for patients who had undergone primary induction chemotherapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The clinical applications of mammary ductoscopy.

BACKGROUND: Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and biopsy examination of the mammary ductal epithelium where most cancers originate. The procedure can be performed under local anesthesia in the office setting. This article reviews the rationale, current clinical applications, and limitations of MD. METHODS: A literature search was performed using Pubmed for indexed articles published over the past 30 years using the key words "mammary ductoscopy," "breast ductoscopy," "ductal lavage," and "nipple aspiration." The most important articles were analyzed and discussed. RESULTS: MD is a useful diagnostic adjunct in patients with pathologic nipple discharge. Furthermore, it can reduce the number and extent of duct excision surgeries for pathologic nipple discharge. There is a clear need to design prospective clinical trials that evaluate the potential role of MD in breast cancer screening, guiding risk-reducing strategies, and as an adjunct to breast-conservation surgery. CONCLUSIONS: MD is useful in the management of PND, but its potential role in the early detection or management of breast cancer requires further investigation.

Breast Neoplasms↗
PubMed2005

Mammary ductoscopy: current status and future prospects.

BACKGROUND: Mammary ductoscopy (MD) allows direct visualisation of the mammary ducts using sub-millimetre fiberoptic microendoscopes inserted through the ductal opening onto the nipple surface. The sharp clear magnified images are viewed on a video monitor. Such scopes have working channels that allow irrigation and ductal lavage for cytological analysis. MD can be performed under local anaesthesia in the office setting. This article reviews the evolving role of MD in the diagnosis and treatment of intraductal breast disease. METHODS: A literature search was carried out from Pubmed for indexed articles published over the last 30 years using the keywords 'mammary ductoscopy' and 'breast ductoscopy'. RESULTS: The search yielded 27 indexed published articles and reports. Important major reports and studies were reviewed, screened and tracked for other relevant publications. The most important articles were analysed and discussed. The review also includes our published and unpublished original work in the field of MD. CONCLUSIONS: MD is a useful diagnostic adjunct in patients with pathological nipple discharge (PND). Furthermore, it can reduce the number and extent of duct excision operations for PND. However, its potential use in the early detection of breast cancer, guiding breast conserving surgery (BCS) for cancer, therapeutic ablation of intraductal disease, and guiding risk-reducing strategies among high risk women requires further research and evaluation. Future developments include the development of a biopsy kit, combining MD with molecular diagnostic markers and real-time optical biopsy system for the diagnosis of pre-malignant and early malignant disease and radiofrequency for curative ablation of intraductal lesions.

Adolescent↗
PubMed2005

Docetaxel in ovarian cancer.

Docetaxel, a semisynthetic taxane, is a potent inhibitor of cell replication and, similar to paclitaxel, promotes in vitro assembly of stable microtubules and, therefore, prevents the depolymerisation process. Docetaxel has a higher affinity for the tubulin subunit and is associated with a 100-fold greater phosphorylation of BCL-2 inducing apoptosis. Docetaxel in combination with carboplatin demonstrates similar activity to paclitaxel/carboplatin in the upfront management of advanced ovarian cancer with less neurological, but greater haematological toxicity. This article reviews the rationale and indications for the use of docetaxel in ovarian cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2004

A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype.

A novel protein MGC5306 has been identified in yeast-two-hybrid analysis by screening a HeLa cDNA library with a truncated DNA polymerasebeta (polbetaDelta) as bait. The polbetaDelta is expressed in various types of cancers. Co-immunoprecipitation-Western blot analysis confirms not only its interaction with polbetaDelta but also with wild-type polbeta. Binding to polbeta indicates potential function of MGC5306 in repair pathway. Transfection of cells with MGC5306-GFP and Western blot analysis with anti-MGC5306 antibody reveal its nuclear localization. MGC5306 is expressed in human carcinomas and tumor cell lines but not in normal tissues, suggesting MGC5306 is most likely involved in carcinogenesis. An antigrowth activity and modulations of cell cycle events are identified in cells expressing siRNAMGC5306.

Amino Acid Sequence↗
PubMed2004

Prevention of vesicovaginal fistulas after laparoscopic hysterectomy with electrosurgical cystotomy in female mongrel dogs.

OBJECTIVE: Using a previously described animal model, we sought to compare 3 methods of double-layer cystotomy repair to each other and to single-layer repair in the prevention of vesicovaginal fistula formation. STUDY DESIGN: Twenty-four female mongrels, which were divided into 3 groups, underwent laparoscopic hysterectomy followed by monopolar electrosurgical cystotomy. Group 1 had simple 2-layer cystotomy repair with interrupted 2-0 polyglactin sutures; group 2 had resection of tissue 5 mm beyond the visible electrosurgical burn margin followed by 2-layer closure, and group 3 had interposition of an omental flap after 2-layer closure. Animals were killed at least 27 days after the operation, and a careful evaluation for vesicovaginal fistulas was undertaken by retrograde bladder filling. Group results were compared with one another and to a historic control group of 8 dogs that had undergone cystotomy repair with single-layer closure. RESULTS: All groups were similar in preoperative and necropsy weight. Bladder perforation occurred in 1 dog in group 1 on postoperative day 3; necropsy revealed perforation in the area of electrosurgical thermal spread with intact sutures. No vesicovaginal fistulas were noted in any of the study dogs (0/23 dogs; 95% CI, 0-12.7%) compared with 2 of 8 dogs (25%) that underwent single-layer closure (95% CI, 0-55%; P=.06). CONCLUSION: Double-layer repair appears to be superior to single-layer repair for the prevention of vesicovaginal fistulas after monopolar cystotomy. The benefit of electrosurgical burn margin excision or omental flap interposition remains unclear, but both are accomplished easily with little risk and may play a role in fistula prevention.

Animals↗
PubMed2004

Phase 2 trial of carboplatin, paclitaxel, and irinotecan in ovarian, fallopian tube, and primary peritoneal cancers.

OBJECTIVE: Our goal in this nonrandomized phase 2 trial was to evaluate the toxicity and obtain preliminary data on the potential efficacy of a novel three-drug combination regimen (carboplatin-paclitaxel-irinotecan) when employed as initial therapy of advanced ovarian cancer or as second-line treatment in the setting of a prolonged (>or=12 months) treatment-free interval. METHODS: Patients with a histologically confirmed diagnosis of advanced ovarian cancer, primary adenocarcinoma of the peritoneum, or fallopian tube cancer were enrolled in the study. Patients received carboplatin (AUC 5), paclitaxel (150 mg/m(2) over 3 h), and irinotecan (100 mg/m(2) over 90 min). The three-drug combination was initially administered on an every 21-day schedule, but due to toxicity was subsequently changed to a 28-day program. RESULTS: A total of 30 patients were enrolled into this phase 2 trial. Twenty-three patients were chemotherapy naive, while 7 had received prior chemotherapy. Seventeen patients completed all six cycles of treatment. Eight patients (27%) were removed from the study after a median of three cycles due to toxicities. Seventeen patients (57%) experienced grade 4 neutropenia, with three individuals requiring hospitalization for neutropenic fever and dehydration. Grades 3 and 4 thrombocytopenia were experienced by three patients each. The principal nonhematologic toxicities were diarrhea (grade 3: three patients) and fatigue. The overall objective clinical response rate was 83%. CONCLUSIONS: The combination of carboplatin-paclitaxel-irinotecan can be administered to women with advanced ovarian cancer with significant, but overall acceptable toxicity. Modification of the regimen from a 3-week to a 4-week schedule permits a greater percentage of patients to complete the program without experiencing excessive toxicity. The overall objective response rate observed in this trial is comparable to other combination regimens employed in this setting. Defining a place for this three-drug program in the standard management of ovarian cancer will require the conduct of an appropriately designed randomized trial.

Adult↗
PubMed2003

Phase 2 trial of pegylated liposomal doxorubicin in advanced endometrial cancer.

PURPOSE: To evaluate the efficacy and toxicity of pegylated liposomal doxorubicin in patients with advanced endometrial cancer. METHODS: Pegylated liposomal doxorubicin was administered at a dose of 40 mg/m2, and repeated on an every 28-day schedule. RESULTS: A total of 19 patients were enrolled in this phase 2 trial. Fourteen patients had received prior chemotherapy (carboplatin/paclitaxel-9; cisplatin/paclitaxel-3; single agent paclitaxel-2), seven prior radiation therapy, and three prior hormonal therapy. No patients had previously received doxorubicin. Two patients (11%) developed grade 1 hand-foot syndrome following treatment with pegylated liposomal doxorubicin. There were no episodes of cardiac dysfunction (>10% reduction in baseline ejection fraction). Three patients required hospitalization for nausea, vomiting, anemia, and dehydration. Only 2 (11%) patients required dose reduction. Four of 19 patients (21%; 95% CI: 3-39%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy (duration of responses: 2 months, 3 months, 4 months, 6+ months). CONCLUSION: The pegylated liposomal doxorubicin regimen employed in this trial exhibited an acceptable toxicity profile (cardiac dysfunction, hand-foot syndrome). Definite, although modest, antineoplastic activity in a patient population with recurrent or advanced endometrial cancer was documented.

Aged↗
PubMed2003

Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy.

OBJECTIVE: The objective of the study was to evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia. METHODS: Forty-five patients with high-risk gestational trophoblastic tumors received 257 EMA-CO treatment cycles between 1986 and 2001. Twenty-five were treated primarily with EMA-CO because of the presence of one or more high-risk factors and 20 were treated with EMA-CO secondarily after failure of single-agent chemotherapy. Patients who had incomplete responses or developed resistance to EMA-CO were treated with drug combinations employing cisplatin and etoposide with or without bleomycin or ifosfamide. Adjuvant surgery and radiotherapy were used in selected patients. Survival, clinical response, and toxicity were analyzed retrospectively. RESULTS: The overall survival rates was 91% (41/45); survival rates were 92% (23/25) for primary treatment and 90% (18/20) for secondary treatment with EMA-CO. Of the 45 patients treated with EMA-CO, 32 (71%) had a complete clinical response, 9 (20%) developed resistance but were subsequently placed into remission with cisplatin-based chemotherapy, and 4 (9%) died of widespread metastatic disease. Clinical complete response to EMA-CO was significantly influenced by duration of disease from antecedent pregnancy to treatment (<6 months, 84%, vs >6 months, 43%), metastatic site (lung and pelvis, 73%, vs other, 40%), and WHO score (< or =7, 96%, vs >7, 36%). The EMA-CO chemotherapy regimen produced no life-threatening toxicity, caused grade 3-4 hematologic toxicity in 1.6% of cycles, and was associated with neutropenia necessitating a 1-week delay in treatment in only 13.5% of cycles. CONCLUSION: EMA-CO chemotherapy is a well-tolerated and highly effective treatment for high-risk gestational trophoblastic neoplasia, yielding a 71% complete response rate and a 91% survival rate in this series.

Adolescent↗
PubMedDate not supplied

Myeloma of the breast.

Explore the source record for details and available documents.

Breast Neoplasms↗
PubMedDate not supplied

Ductoscopy-assisted microdochectomy.

Until 10 years ago, examination of the ductal system of the breast required excision of all the major ducts, in a block of tissue. With mammary ductoscopy, direct visualization of the ducts in vivo has been possible. In the present series of 40 cases, ductoscopy was used to guide the infusion of methylene blue dye, through the endoscope, to find the index duct, which is then removed through a small incision just inside the areola.

Breast Neoplasms↗
PubMedDate not supplied

The potential role of breast ductoscopy in breast cancer screening.

Breast cancer remains the most common malignancy among women in the Western world. Mammography, which is currently the main screening modality for early detection, has a low positive predictive value of only 25%, especially in young women with very dense breasts. Therefore, new screening approaches are needed for the early detection of breast cancer in all age groups. Mammary ductoscopy (MD) is a newly developed endoscopic technique that allows direct visualization and biopsy of the mammary ductal epithelium where most cancers originate. The procedure can be performed under local anesthesia in the office setting. At present, MD is used as a diagnostic adjunct in patients with pathological nipple discharge and to guide duct excision surgery. This article focuses on the potential of this technique in breast cancer screening and highlights its limitations in this context.

Breast Neoplasms↗