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P J DiSaia

Publications and source records attributed to P J DiSaia.

At least 19 recordsLinked to original sources
PubMed2001

Estrogen replacement therapy in endometrial cancer patients: a matched control study.

OBJECTIVE: To determine if estrogen replacement therapy, in women with a history of endometrial cancer, increases the risk of recurrence or death from that disease. METHODS: Two hundred forty-nine women with surgical stage I, II, and III endometrial cancer were treated between 1984 and 1998; 130 received estrogen replacement after their primary cancer treatments and 49% received progesterone in addition to estrogen. Among this cohort, 75 matched treatment-control pairs were identified. The two groups were matched by using decade of age at diagnosis and stage of disease. Both groups were comparable in terms of parity, grade of tumor, depth of invasion, histology, surgical treatment, lymph node status, postoperative radiation, and concurrent diseases. The outcome events included the number of recurrences and deaths from disease. RESULTS: The hormone users were followed for a mean interval of 83 months (95% confidence interval [CI] 71.0, 91.4) and the nonhormone users were followed for a comparable mean interval of 69 months (CI 59.1, 78.7). There were two recurrences (1%) among the 75 estrogen users compared with 11 (14%) recurrences in the 75 nonhormone users. Hormone users had a statistically significant longer disease-free interval than nonestrogen users (P =.006). CONCLUSION: Estrogen replacement therapy with or without progestins does not appear to increase the rate of recurrence and death among endometrial cancer survivors.

Adenocarcinoma↗
PubMed2001

Bowel resection at the time of primary cytoreduction for epithelial ovarian cancer.

BACKGROUND: The purpose of this study was to determine the morbidity and survival associated with bowel resection at the time of primary cytoreductive surgery for ovarian cancer. STUDY DESIGN: We reviewed all patients undergoing bowel resection by gynecologic oncology faculty at the time of primary cytoreduction for advanced epithelial ovarian cancer diagnosed between 1983 and 1995. RESULTS: There were 105 patients meeting the above criteria. The median age was 65 years (range 34 to 85 years). There were 76 stage III and 25 stage IV cancers. The primary indication for bowel resection was tumor debulking in 92% of the patients. Seventy patients had segmental resection of the colon only, and 22 patients underwent resections that included the large and small bowels. Mean operating time was 260 minutes and mean estimated blood loss was 1,447 mL. Thirty-three (31%) patients were optimally cytoreduced to less than 1 cm residual disease. Ten patients experienced major complications directly related to bowel resection, including bowel fistula (4 patients), early postoperative bowel obstruction (5 patients), and stomal hernia (1 patient). Other morbidity included ileus for more than 10 days (18 patients), cardiac complications (17 patients), pneumonia (8 patients), sepsis (5 patients), and thromboembolism (4 patients). Six patients died and five patients required reexploration within 30 days of operation. Patients with preoperative bowel obstruction and suboptimal residual disease were more likely to have postoperative morbidity. Median survival in the optimally debulked patients was 35 months compared with 18 months in patients suboptimally cytoreduced (p = 0.006). Multivariate analysis demonstrated that optimal debulking (p = 0.009) and platinum chemotherapy (p = 0.00006) were independently associated with improved survival. Age, International Federation of Gynecologia Oncologists stage, American Society of Anesthesiologists class, and paclitaxel chemotherapy did not influence survival. CONCLUSIONS: In patients undergoing bowel resection at the time of primary cytoreduction for ovarian cancer, optimal cytoreduction to less than 1 cm residual disease results in improved survival. Morbidity is common but is comparable to other published series of ovarian cancer patients undergoing primary cytoreductive surgery without bowel resection. Additionally, patients with preoperative bowel obstruction and suboptimal residual disease are more likely to have serious morbidity.

Adult↗
PubMed2001

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.

OBJECTIVE: The aim of this study was to determine whether 2 photosensitizers, benzoporphyrin-derivative monoacid ring and 5-aminolevulinic acid, are selectively absorbed by dysplastic cervical cells after topical administration. STUDY DESIGN: This phase I clinical trial involved 18 women with biopsy-proven cervical intraepithelial neoplasia at the Beckman Laser Institute, Irvine, Calif. Colposcopically directed cervical biopsy specimens obtained after 1.5, 3, or 6 hours of exposure to a randomly assigned photosensitizer were evaluated for selective drug absorption with hematoxylin and eosin staining and fluorescence microscopy. RESULTS: After exposure to 5-aminolevulinic acid, cervical tissue showed maximal fluorescence in dysplastic cells relative to normal cells, with negligible stromal fluorescence. According to our detection methods benzoporphyrin-derivative monoacid ring demonstrated nonselective, diffusion-driven uptake, with fluorescence appearing in the superficial cells, followed by nonselective drug absorption in the remaining cells and stroma of the epithelium. CONCLUSION: Our data demonstrated selective absorption of 5-aminolevulinic acid by dysplastic cervical cells. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical intraepithelial neoplasia with photodynamic therapy.

Absorption↗
PubMed2001

Recent advancements in the treatment of epithelial ovarian cancer.

Important advances in the management of advanced epithelial ovarian cancer have been made in recent years, with much of the knowledge emanating from clinical trials conducted by the Gynecological Oncology Group (GOG). This monograph reviews the trials that have defined current clinical practice and summarizes some innovative techniques and promising new drugs for the future

Antineoplastic Agents↗
PubMed2001

Bilateral pheochromocytoma in pregnancy heralding multiple endocrine neoplasia syndrome IIA. A case report.

BACKGROUND: Multiple endocrine neoplasia syndrome type IIA (MEN IIA) has rarely been encountered in pregnancy. CASE: A 22-year-old, nulliparous woman developed bilateral pheochromocytomas during pregnancy. This finding aroused suspicion for MEN IIA, and close endocrinologic follow-up was arranged. Four years later, hyperparathyroidism developed, and the diagnosis was established. The patient underwent prophylactic total thyroidectomy with parathyroid exploration. CONCLUSION: This was the first case of MEN IIA in pregnancy in which the diagnosis was established prior to the development of medullary thyroid cancer, thereby allowing prophylactic thyroidectomy. The presence of bilateral neoplastic disease in young patients may be indicative of a hereditary predisposition to malignancy.

Adrenal Gland Neoplasms↗
PubMed2000

Development and assessment of a general theory of cervical carcinogenesis utilizing a severe combined immunodeficiency murine-human xenograft model.

OBJECTIVE: Currently, we lack a theoretical explanation for why squamous cell cervical cancer develops predominantly in specific sites (i.e., along the squamocolumnar junction). We therefore implanted human cervical tissues containing the transformation zone in severe combined immunodeficiency (SCID) mice and studied morphology, steroid effects, gene expression, and human papillomavirus (HPV) factors. METHODS: Normal and dysplastic human cervical tissues (3 x 2 mm) were placed subcutaneously in SCID-beige mice and later assessed by in situ hybridization for HPV 16/18 DNA and by immunohistochemistry for expression of CD31, keratin, proliferating-cell nuclear antigen, HPV 16 E6, p53, and Notch-1 (a binary cell fate determination protein). Some normal tissues were implanted with either a 90-day release 1.7-mg 17beta-estradiol pellet or a 5-mg tamoxifen pellet; others were infected prior to implantation with human recombinant adenovirus 5 vector containing a human cytomegalovirus promoter-driven beta-galactosidase gene and later assessed by X-gal staining. RESULTS: Murine and human vessels formed anastomoses by 3 weeks. For at least 11 weeks, normal tissue retained the transformation zone and normal cell-type-specific keratin expression and exhibited normal proliferation; Notch-1 was present only in the basal cell layer. Dysplastic tissues exhibited koilocytosis, increased levels of cellular proliferation, and aberrant keratin, p53, and Notch-1 expression; HPV 16/18 DNA and HPV 16 E6 protein were detected for at least 6 weeks. Squamous metaplasia of normal cervical epithelium resulted from estrogen exposure, and a predominant columnar differentiation pattern was associated with tamoxifen administration. Through stable adenovirus infection, beta-galactosidase was expressed for at least 6 weeks. CONCLUSIONS: This small manipulatable xenograft model maintains normal and dysplastic human cervical epithelium through neovascularization. Neoplastic tissue retains HPV 16/18 DNA and a premalignant phenotype, including elevated levels of cellular proliferation and aberrant keratin, p53, and Notch-1 expression. These attributes constitute essential features of a biologic model through which one may study HPV-mediated human disease and may be superior to cell culture and transgenic murine systems. Furthermore, this may serve as a model for gene therapy. Finally, we suggest that the normal cervical epithelium is maintained through putative interactions between the Notch locus and cell cycle growth regulators such as p53 and pRb. Neoplastic cervical epithelium may arise through disruption of this pathway. This theory may be testable in our animal model.

Animals↗
PubMed2000

Biomarker conservation in primary and metastatic epithelial ovarian cancer.

PURPOSE: The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS: Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied. RESULTS: A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Breast cancer survival and hormone replacement therapy: a cohort analysis.

Controversy exists regarding the safety of hormone replacement therapy (HRT) after a diagnosis of breast cancer. The objective of this study is to perform a matched cohort analysis to evaluate the impact of HRT on mortality in breast cancer survivors. Patients with breast cancer who received HRT after diagnosis of breast cancer were identified. Control subjects were identified from the regional cancer registry. Matching criteria included age at diagnosis, stage of breast cancer, and year of diagnosis. Controls were selected only if they were alive at the time of initiation of HRT of the matched case. Only subjects not included in a previously reported matched analysis were selected. One hundred twenty-five cases were matched with 362 controls. Ninety-eight percent (123/125) of the cases received systemic estrogen; 90/125 (72%) also received a progestational agent. The median interval between diagnosis of breast cancer and initiation of HRT was 46 months (range 0-401 months). The median duration of HRT was 22 months (range 1-357 months). The risk of death was lower among the HRT survivors; odds ratio 0.28 (95% confidence interval 0.11-0.71). This analysis does not suggest that HRT after the treatment of breast cancer is associated with an adverse outcome.

Breast Neoplasms↗
PubMed1999

Phase II trial of vinorelbine in recurrent and progressive epithelial ovarian cancer.

OBJECTIVE: A phase II, multicenter trial was conducted to define the efficacy and safety of vinorelbine (Navelbine (vinorelbine tartrate) injection, NVB) in the treatment of advanced epithelial ovarian cancer (EOC). METHODS: Patients with persistent or recurrent EOC who had received one prior platinum-based chemotherapy regimen were eligible. NVB was administered at 30 mg/m2 as a weekly outpatient intravenous infusion. RESULTS: Using an intent-to-treat analysis of the 38 patients who received at least one dose, 11(29%, 95% confidence limits 15-46%) objective responses (4 complete, 7 partial) were observed. The median duration of response was 19 weeks. For all 38 patients, the median time to treatment failure and median survival were 12 and 60 weeks, respectively. Four of the 12 patients with platinum-resistant disease responded, while 7 of the 24 patients with platinum-sensitive disease responded. Toxicity was evaluable in all 38 patients. During course 1, 15 patients required dose reduction and 21 required dose delays. Grade 3-4 granulocytopenia occurred in 23 (62%) of 37 reporting patients. Grade 3-4 anemia and thrombocytopenia occurred in 16 and 5%, respectively. The most common nonhematologic toxicities were nausea (grade 3 or less, in 34%), constipation (grade 3 or less, in 29%), and asthenia (grade 2 or less, in 24%). No life-threatening adverse effects were reported. CONCLUSIONS: NVB is an effective, palliative agent for women with recurrent EOC. Dose-limiting granulocytopenia is substantial, yet manageable.

Adult↗
PubMed1999

Management of ovarian cancer in patients older than 80 years of Age.

OBJECTIVE: The objective of this study was to examine the treatment, associated morbidity, and survival in very elderly patients with epithelial ovarian cancer. METHODS: A retrospective analysis of patients 80 years of age and older treated for epithelial ovarian cancer by the Gynecologic Oncology faculty at the University of California Irvine was performed. RESULTS: Eighteen patients were older than 80 years of age at the time of diagnosis of ovarian cancer. Median age was 83 years (range 80-86 years). There were 2 stage I, 10 stage IIIC, 4 stage VI, and 2 unstaged patients. One patient had a tumor of low malignant potential, 4 patients had grade II tumors, and 10 patients had tumors that were grade III. Eighty-three percent of patients had one or more preexisting medical illnesses. Cardiac disease, stroke, and hypertension were most common. Sixteen of 18 patients (88%) underwent primary debulking surgery. American Society of Anesthesiologists physical status classification was as follows: 7/16 (44%) class II, 6/16 (38%) class III, and 2/16 (13%) class IV. The procedures performed included 16 bilateral salpingo-oophorectomies, 11 total abdominal hysterectomies, 16 omentectomies, 3 lymph node dissections, and 7 bowel resections. Four (25%) patients were optimally cytoreduced to <1 cm of residual disease. Seventy-five percent of surgical patients received blood transfusions of 2 or more units PRBC. Mean EBL was 600 cc (range 200-4200 cc). Thirty-eight percent of patients experienced major postoperative morbidity. There were 7 patients with postoperative congestive heart failure, 3 with sepsis, 1 with aspiration pneumonia, and 2 postoperative deaths. Seventy-five percent of patients spent time in the intensive care unit. Median number of days was 3 (range 1-22 days). Mean postoperative stay was 8 days (range 6-57 days). Sixty-five percent of patients were discharged to home. The other patients were discharged to intermediate care facilities or nursing homes. Eighty-three percent of patients received chemotherapy. Of the 10 patients (63%) receiving adjuvant chemotherapy, the mean interval from surgery to initiation of therapy was 3 weeks (range 1-4 weeks). Overall median survival was 6 months (range 1-45 months). Median survival in patients with optimal debulking was 32.5 months (range 7-45 months) compared to 3.5 months (range 1-41 months) in patients suboptimally debulked. CONCLUSIONS: In patients older than 80 years of age who undergo debulking surgery for ovarian cancer, serious medical comorbidity and advanced ASA status are common. Despite aggressive surgical effort and frequent blood transfusions, optimal debulking to less than 1 cm is achieved in only 25% of patients. Impressive morbidity and mortality occurs in this group of patients, but most patients are discharged to home and are able to receive postoperative chemotherapy.

Age Factors↗
PubMed1999

Long-term consequences following conservative management of epithelial ovarian cancer in an infertile patient.

A 35-year-old woman with primary infertility underwent an ovarian cystectomy for a 5 x 4 cm left adnexal mass. There was no macroscopic evidence of metastatic disease. The final pathology report revealed a poorly differentiated serous cystadenocarcinoma. Because the patient desired to retain child-bearing capacity, she refused a surgical staging of her ovarian cancer. She elected to receive combination chemotherapy. This was then followed by a negative reassessment laparotomy. The patient was diagnosed with recurrent, metastatic ovarian carcinoma 10 years later.

Adult↗
PubMed1999

Interstitial brachytherapy for vaginal recurrences of endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.

Aged↗
PubMed1999

Fertility-sparing treatment of patients with ovarian cancer.

Ovarian malignancies in reproductive age women often provide the physician and patient with a management dilemma. Many investigators have proposed conservative management in early-stage disease. This article provides evidence supporting fertility-sparing management in young women with early ovarian malignancies.

Adenocarcinoma↗
PubMed1999

Young age as a prognostic factor in cervical cancer: results of a population-based study.

OBJECTIVE: Our goal was to use population-based data to determine the difference in 5-year survival in women diagnosed with cervical cancer between those aged 18-34 years and those aged 40-60 years. STUDY DESIGN: The SEER (Surveillance, Epidemiology, and End Results) public-use database, 1973-1994, was used for this investigation. Only subjects with cervical carcinoma diagnosed between 1988 and 1990 were included. Subjects were stratified on age at diagnosis (<35 years or 40-60 years), clinical stage, histologic type, race-ethnicity, and grade. RESULTS: Two thousand cases of invasive cervical cancer were identified. The younger subgroup of patients was diagnosed with earlier-stage disease more frequently than the older group (P =.0001). When adjustments were made for non-cervical cancer causes of death, there was no difference in 5-year survival between the 2 cohorts. African American women had a poorer 5-year survival (P =.02) CONCLUSION: There was no overall difference in survival between the 2 cohorts when appropriate adjustments were made for cause of death and for stage, histologic type, and grade of disease.

Adenocarcinoma↗
PubMed1999

Significance of true surgical pathologic staging: a Gynecologic Oncology Group Study.

OBJECTIVE: The object of the study was to determine the true surgical pathologic disease extent in patients with clinical stage II adenocarcinoma of the endometrium. STUDY DESIGN: As part of a Gynecologic Oncology Group surgical pathologic protocol of patients with adenocarcinoma of the endometrium, patients with clinical stage II cancers were evaluated. Among >1000 patients with early stage disease entered into this protocol group study, 148 were in clinical stage II. All patients underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, and selective pelvic and para-aortic lymphadenectomy as the primary therapy. Surgical pathologic material was evaluated to determine true extent of disease. RESULTS: Only 66 of 148 (45%) of patients in clinical stage II had cancer in the cervix. Fifty-seven patients had disease limited to the upper fundus and 25 had disease extending into the lower uterine segment but not into the cervix. Among the 66 patients with disease in the cervix, only 35 had disease limited to the uterus whereas 31 patients had extrauterine disease (lymph nodes, adnexa, etc). Thus among 148 patients with diagnoses of clinical stage II disease only 35 (24%) in fact had true surgical stage II cancer. CONCLUSION: Clinical diagnosis of stage II adenocarcinoma of the uterus is a poor reflection of true surgical stage II cancer. Only when true extent of disease is known can optimally definitive therapy be determined.

Adenocarcinoma↗