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Biomedical subjects

E G Silva

Publications and source records attributed to E G Silva.

At least 19 recordsLinked to original sources

Synthesis and pharmacological properties of TOAC-labeled angiotensin and bradykinin analogs.

Angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label were synthesized by solid phase methodology. Ammonium hydroxide (pH 10, 50 degrees C, l h) was the best means for reverting nitroxide protonation occurring during peptide cleavage. EPR spectra yielded rotational correlation times for internally labeled analogs that were nearly twice as large as those of N-terminally labeled analogs. Except for TOAC(1)-AngII and TOAC(0)-BK, which showed high intrinsic activities, other derivatives were inactive in smooth muscle preparations. These active paramagnetic analogs may be useful for conformational studies in solution and in the presence of model and biological membranes.

Ammonium Hydroxide↗

Vessels within vessels in the myometrium.

We have encountered a peculiar vascular architecture in the myometrium wherein arteries are found free-floating within cleft-like spaces. Using different colored dye injections in the uterine arteries and veins, we demonstrated that these spaces are venous channels. This was confirmed by immunoperoxidase staining for CD34, which enhanced the cells lining these spaces. A review of 81 hysterectomy specimens showed that this vascular architecture was present in 42 cases (52%), while it was identified in the parenchyma of only two mastectomy specimens among the 45 specimens from different organs studied. A strong association existed between the presence of this architecture and history of menorrhagia (p = 0.0116). This peculiar vascular architecture might be important in the pathogenesis of menorrhagia and the development of intravenous leiomyomatosis. Pathologists should also be able to recognize these spaces as vascular channels in the event that malignant cells are identified within them.

Adult↗

Desmoplastic small round cell tumor: report of a case presenting as a primary ovarian neoplasm.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an intra-abdominal malignancy that typically has extensive peritoneal spread at the time of diagnosis. We report a case of DSRCT with involvement of the ovary and omentum as well as an elevated CA-125 level at presentation. CASE: A 23-year-old female presented to another institution with a pelvic mass and a CA-125 level of 140 U/ml. During tumor reductive surgery the right ovary, omentum, and liver were found to be involved. Initial histologic examination favored an undifferentiated small cell carcinoma of the ovary. The patient received two cycles of Taxol and cisplatin chemotherapy and was referred to the University of Texas M. D. Anderson Cancer Center. Upon review of the pathology material at the time of the referral, a diagnosis of DSRCT was made. Despite two additional cycles of chemotherapy, the tumor progressed, and the patient returned home. CONCLUSION: DSRCT may mimic an ovarian primary tumor by presenting with involvement of the ovary and an elevated CA-125 level, and should be included in the differential diagnosis of ovarian neoplasms in young patients.

Adult↗

Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors.

The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.

Adult↗

Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival.

BACKGROUND: Merkel cell carcinoma is a rare malignant neoplasm of the skin that most often arises in the head and neck region. Despite the innocuous appearance of the primary lesion, Merkel cell carcinoma often has an aggressive clinical course with frequent locoregional recurrences and distant metastases. We evaluated the association of the width of surgical margins and the use of postoperative radiation therapy with locoregional control and survival rates. METHODS: The medical records of 66 patients with head and neck Merkel cell carcinoma seen between 1945 and 1995 were retrospectively reviewed. The Fisher exact test was used to compare outcomes. Kaplan-Meier survival curves were constructed. RESULTS: Eighteen patients for whom there was adequate information were divided into the following groups according to the width of their surgical margins: smaller than 1 cm, 1 to 2 cm, and larger than 2 cm. No statistical difference in locoregional control or survival was found among these groups owing to the small patient population. In contrast, a comparison of the patients who did (n = 26) and did not (n = 34) receive postoperative radiation therapy revealed a significant difference in local (3 [12%] vs 15 [44%], respectively; P<.01) and regional (7 [27%] vs 29 [85%], respectively; P<.01) recurrence rates. There was, however, no significant difference in the disease-specific survival between these groups (P = .30). Distant disease developed in 36% of all patients regardless of therapy. CONCLUSIONS: Any effect of the width of surgical margins on outcome was not detectable in the small number of patients analyzed. The use of postoperative radiation therapy was associated with a significant improvement in locoregional control. There was no detectable influence of the type of initial therapy on the rates of distant metastases or on survival. Future therapeutic innovations should be directed toward controlling the development of distant metastases in patients with Merkel cell carcinoma.

Adult↗

Serous tumors involving extra-abdominal/extra-pelvic sites after the diagnosis of an ovarian serous neoplasm of low malignant potential.

The involvement of extra-abdominal/extra-pelvic sites by serous tumors after the diagnosis of an ovarian serous neoplasm of low malignant potential is extremely rare. In this study we present the clinicopathologic features of 12 such cases seen at our institution during a period of 19 years (1980-1999). The patients' age ranged from 19 to 50 years (mean 33 years). By FIGO staging the original ovarian tumors were distributed as follows: stage I, 4; stage II, 2; stage III, 5; unknown stage, 1. All patients were treated surgically. Ten patients also received adjuvant therapy (radiotherapy, 2; chemotherapy and radiotherapy, 4; chemotherapy, 3; intraperitoneal 32P, 1). The interval between the diagnosis of the ovarian neoplasm and the subsequent tumor involving an extra-abdominal/extra-pelvic site ranged from 4 to 240 months (mean 124 months). Sites of extra-abdominal/extra-pelvic involvement and the number of cases were as follows: left neck lymph nodes (LNs), 4; left and right neck LNs, 1; pleura, 2; lung, 1; mediastinum, 1; chest wall, 1; axillary and chest LNs, 1; and vertebral body, 1. Eight patients were treated with chemotherapy, 1 with radiotherapy, 2 with chemotherapy and radiotherapy, and 1 with surgery alone. Follow-up ranging from 5 months to 18 years was available in 11 patients. Six patients died of disease and 5 patients were alive with no evidence of disease. In this small series of cases, no definitive clinical or pathologic feature related to the occurrence of extra-abdominal/extra-pelvic serous tumors was found. Based on the LN involvement and the endosalpingiosis seen in some cases, these tumors might develop from circulating neoplastic serous cells or from areas of endosalpingiosis involving extra-abdominal/extra-pelvic sites.

Adult↗

Immunohistochemical analysis of clear cell carcinoma of the gynecologic tract.

Clear cell carcinoma of the gynecologic tract has been defined in terms of its clinical and histologic features; however, its immunophenotypic profile has not been fully characterized. Seventeen cases of primary clear cell carcinoma from various sites within the female genital tract (11 ovary, 5 uterus, 1 vagina) were analyzed by immunohistochemistry. These tumors were assessed for the expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), low and high molecular weight cytokeratin, (CAM5.2 and 34 beta E12, respectively), carcinoembryonic antigen (CEA), Leu-M1, vimentin, estrogen receptor (ER), progesterone receptor (PR), bcl-2, p53, HER-2/neu, and CA-125. The characteristic immunoprofile for all sites was positivity for CK7, CAM5.2, 34 beta E12, CEA, Leu-M1, vimentin, bcl-2, p53, and CA-125; variably positivity for ER and HER-2/neu; and negativity for CK20 and PR. For comparison, two cases of urologic clear cell carcinoma (1 bladder, 1 urethra) were also studied, and their profile was found to be similar to the gynecologic cases. Aside from minor differences, clear cell carcinoma appears to have the same immunophenotype regardless of whether it originates in the endometrium, ovary, or genitourinary tract. Much of its profile is similar to other gynecologic adenocarcinomas, but some of the markers studied may be useful in the differential diagnosis of this tumor.

Adenocarcinoma, Clear Cell↗

Ovarian mixed-epithelial carcinomas with a microcystic pattern and signet-ring cells.

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.

Adult↗

Parameters of differentiation and proliferation in adult granulosa cell tumors of the ovary.

We evaluated parameters of cell differentiation and proliferation to improve prognostication of ovarian adult granulosa cell tumors. Recurrent tumors (n = 10, REC group) and nonrecurrent tumors (n = 30, NED group) were compared in terms of cellular atypia, nuclear area, p53 overexpression, ploidy, DNA index, mitosis count, S-phase fraction, and nucleolar organizer region number and area per cell. Cellular atypia was significantly more frequent in REC than NED tumors (50% versus 13%; P = .03). Mean nuclear area was significantly larger in the REC than in the NED group (44 microm2 versus 36 microm2; P = .006). Mitotic count was significantly higher in REC than NED tumors (mean of 4.8 versus 1.7; P = .004). S-phase fraction and ploidy did not predict outcome: neither did nucleolar organizer region numbers and area per cell, or p53 overexpression. Cellular atypia and mitotic count may help in determining the prognosis of adult granulosa tumors of the ovary. The histochemical parameters evaluated did not provide additional information.

Adult↗

Outcome and reproductive function after conservative surgery for borderline ovarian tumors.

OBJECTIVE: To study reproductive function and disease outcome in women with borderline ovarian tumors who were treated with conservative surgery. METHODS: Patients with borderline ovarian tumors were identified from institutional databases. Patients were eligible if they had pathologically confirmed borderline ovarian tumors, no prior sterilization, no history of radiation therapy, retained their uterus and ovarian tissue, and were younger than age 45. Information was acquired by retrospective medical record review and patient interview. RESULTS: Forty-three patients met the eligibility criteria. The median age was 25 years, with a range of 15-39 years. Twenty-six patients had serous tumors, and 17 had mucinous tumors. Fifteen had stage I disease, three had stage III, and 25 were unstaged. Follow-up was available for all patients (median, 5.7 years). Twenty-nine remained disease-free, and 14 developed a new primary lesion/recurrence, with a median time to recurrence of 39.3 months. Recurrence was more frequent in patients treated with ovarian cystectomy than in those treated with oophorectomy alone (58% compared with 23%) (P <.04). After treatment, 29 of 36 patients (81%) retained normal menstrual cycles, and 12 of 24 patients attempting pregnancy conceived 25 pregnancies. Most patients were highly satisfied with conservative surgery. CONCLUSION: Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Although the rate of new lesion/recurrence is relatively high, especially in those treated with ovarian cystectomy, mortality from cancer remains low. Many patients who desire pregnancy are able to conceive and deliver healthy offspring after conservative surgery.

Adolescent↗

Retrograde endopyelotomy using an original home-made diathermy probe.

PURPOSE: To describe an easily home-made diathermy probe for the performance of retrograde endopyelotomies using a small-caliber rigid ureteroscope. METHODS: The diathermy probe is easily built by putting a rigid guidewire through a 5F ureteral catheter, the distal tip being naked and slightly bent. The other end is linked to the electric generator. Among a total of 24 retrograde endopyelotomies performed to treat ureteropelvic junction obstruction in the last 7 years, five were done using this device. RESULTS: Surgery with the probe took an average of 30 minutes. There were no complications, and, as of today, all cases are successes. CONCLUSION: This device allows the performance of retrograde endopyelotomy using a small-caliber ureteroscope. Long-term results will presumably match the good results obtained using the larger-caliber ureteroscopes with the classic cold knife.

Adolescent↗

Non-Hodgkin's lymphoma involving the vagina: a clinicopathologic analysis of 14 patients.

Non-Hodgkin's lymphomas (NHL) uncommonly involve the vagina. In this study, 14 NHL involving the vagina are reported. Eight cases were stage IE or IIE and are presumed to be primary. The mean age of these eight patients at presentation was 42 years (range, 26-66 yrs), and four of eight patients complained primarily of vaginal bleeding. Histologically, all eight neoplasms were diffuse large B-cell lymphoma (DLBCL). Clinical follow up ranged from 1.8 to 18 years. Six of eight patients were alive without evidence of disease at the last follow up (range, 2.8-21 yrs), one patient died of unrelated causes at 9 years, and one patient died from NHL at 1.8 years. In six patients vaginal involvement was part of systemic disease at diagnosis, either stage IIIE or IV. The mean patient age at the time vaginal involvement was detected was 65 years (range, 49-82 yrs). Four of six patients had vaginal bleeding. Five neoplasms were DLBCL and one tumor was B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Clinical follow up for these patients ranged from 2 weeks to 13 years. Two patients were free of disease after treatment at 4.5 and 13 years, two patients were alive with progressive NHL, one patient died of NHL, and one patient was recently diagnosed. The authors conclude that low-stage (presumably primary) vaginal NHL are DLBCL, tend to occur in younger women, and cause vaginal bleeding. High-stage NHL involving the vagina are usually DLBCL, tend to affect older women, and are relatively more heterogeneous clinically and histologically, but also usually cause vaginal bleeding.

Adult↗

Endometrial carcinoma and non-Hodgkin's lymphoma involving the female genital tract: a report of three cases.

The occurrence of both non-Hodgkin's lymphoma and carcinoma involving the female genital tract of the same patient is rare; we describe three such cases. In case 1, a 56-year-old woman with endometrioid endometrial carcinoma had synchronous follicular lymphoma of the uterus and ovary. In case 2, a 57-year-old woman with diffuse large B-cell lymphoma of the uterine cervix presented 5 years later with an endometrioid endometrial carcinoma. In case 3, a 69-year-old woman with an endometrioid endometrial carcinoma presented with a diffuse large B-cell lymphoma of the vagina 3 years later. In two patients, the non-Hodgkin's lymphoma was unsuspected clinically and would have been missed without biopsy and tissue diagnosis.

Aged↗

Primary ovarian rhabdomyosarcoma associated with clear cell carcinoma of the ovary: a case report and review of the literature.

The clinicopathologic and immunohistochemical findings of a case of coexistent primary ovarian rhabdomyosarcoma and clear cell carcinoma of the ovary are reported. The tumor was detected in a 41-year-old premenopausal woman who had a 1-year history of pelvic pain. On physical examination, a 14.0-cm left adnexal mass was found for which a hysterectomy with bilateral salpingo-oophorectomy and staging biopsies were performed. The tumor was composed of solid and cystic areas, and two distinct microscopic components were identified: clear cell carcinoma and rhabdomyosarcoma. Immunoperoxidase studies demonstrated that the neoplastic cells in the latter component were positive for desmin, muscle-specific actin, and myoglobin. A biopsy taken from the pelvic peritoneum revealed rhabdomyosarcoma (FIGO stage IIB). Despite two cycles of chemotherapy, the disease persisted in the pelvis 4 months after diagnosis.

Actins↗

Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a case report and review of the literature.

We report the clinicopathologic findings of an unusual case of adult granulosa cell tumor with androgenic manifestation in a 13-year-old prepubertal girl. The patient had never had a menstrual period and presented with a 1 year history of hirsutism. Physical examination was only remarkable for an increase in facial and abdominal hair, both with a male pattern of distribution. A pelvic ultrasound demonstrated a 6.0 cm right adnexal cyst. Plasma testosterone and 17-hydroxyprogesterone levels were elevated. The patient initially was treated with monophasic oral contraceptive pills for 3 months and owing to lack of response, she underwent an exploratory laparotomy in which a left ovarian tumor, 7.0 cm in greatest dimension, and a 6.5 cm right paratubal cyst were found. A wedge biopsy of the left ovary and subsequent left oophorectomy with right salpingectomy were performed. No gross evidence of disease outside the ovary was noted. Microscopic examination of the left ovarian tumor revealed the typical features of an adult granulosa cell tumor. No tumor was seen outside the ovary. Six days after surgery, plasma testosterone and 17-hydroxyprogesterone levels were in the normal range. Nine months postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the first case of a prepubertal patient with an adult granulosa cell tumor with androgenic manifestations reported in the English literature.

17-alpha-Hydroxyprogesterone↗

A phase I trial of intravenous melphalan, paclitaxel, and cisplatin plus granulocyte-colony stimulating factor in patients with suboptimal advanced epithelial ovarian carcinoma or peritoneal carcinoma.

BACKGROUND: The primary purpose of this study was to establish the maximum tolerated dose (MTD) of intravenous melphalan in combination with paclitaxel and cisplatin plus granulocyte-colony stimulating factor (G-CSF) in patients with suboptimal advanced epithelial ovarian carcinoma or primary peritoneal carcinoma. METHODS: Patients with suboptimal (>2 cm residual tumor) Stage III or Stage IV epithelial ovarian carcinoma or peritoneal carcinoma were eligible for this Phase I study. In the first stage of the study, the doses of paclitaxel and cisplatin were fixed at 135 mg/m(2) and 75 mg/ m(2), respectively, and the dose of intravenous melphalan was escalated in consecutive cohorts of 3-6 patients depending on toxicity. The planned dose escalation levels of melphalan were 6 mg/m(2), 10 mg/m(2), and 14 mg/m(2). In the second stage of the study, the doses of cisplatin and melphalan were fixed at 75 mg/m(2) and the MTD level, respectively, and the dose of paclitaxel was escalated. The planned dose escalation levels of paclitaxel were 150 mg/m(2), 175 mg/m(2), 200 mg/m(2), 225 mg/m(2), and 250 mg/m(2). G-CSF was administered for 12-19 days with each cycle, and cycles were repeated every 4 weeks for a total of 6 cycles. Other end points included clinical or surgical response, progression free survival, and survival. RESULTS: Between January 1993 and May 1996, 34 women with untreated advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma were treated with 192 cycles of therapy. The MTD of melphalan was 10 mg/m(2), with the dose-limiting toxicity being thrombocytopenia. Paclitaxel was escalated to a dose level of 200 mg/m(2) with a toxicity rate of < 33%. The clinical response rate was 80% in 29 patients with measurable disease. Of 11 patients who underwent second-look surgery, 5 (45%) had a surgical pathologic complete response. The median progression free survival was 16.8 months and the median survival was 32.8 months. CONCLUSIONS: The combination of intravenous melphalan, paclitaxel, and cisplatin was found to have acceptable toxicity and good activity. A Phase II study of this combination appears to be warranted.

Adult↗

The current status of surgical staging of ovarian serous borderline tumors.

BACKGROUND: The purpose of the current study was to evaluate the current practice of surgical staging of ovarian serous borderline tumors. METHODS: Women with a diagnosis of ovarian serous borderline tumors whose pathology slides were sent to the M. D. Anderson Cancer Center for second-opinion diagnostic consultation between 1990-1996 were identified. The original pathology reports and M. D. Anderson Cancer Center consultation reports of 255 cases were reviewed for the frequencies of frozen-section analyses and staging biopsies, biopsy results, the specialty of the surgeon, and hospital type. RESULTS: The majority (78%) of ovarian borderline tumors primarily were encountered and staged by general obstetrician-gynecologists. Overall, 66% of patients had at least 1 staging biopsy performed. Approximately 12% of subjects underwent complete surgical staging, defined as having biopsy samples taken from pelvic and abdominal peritoneum, omentum, and retroperitoneal lymph nodes. Gynecologic oncologists performed complete staging in 50% of cases, obstetrician-gynecologists performed complete staging in 9% of cases, and general surgeons performed complete staging in 0% cases. The overall frequency of a positive staging biopsy was 37%. Approximately 47% (80 of 169) of patients who underwent biopsies were upstaged as a result of positive biopsies, - with 41% (70 of 169) having extrapelvic spread. CONCLUSIONS: Currently, surgical staging for women with ovarian serous borderline tumors remains inadequate, although a significant proportion of patients who undergo staging are noted to have extrapelvic spread.

Adolescent↗

Outcome and reproductive function after chemotherapy for ovarian dysgerminoma.

PURPOSE: To review the outcome for all patients with ovarian dysgerminoma treated at the M.D. Anderson Cancer Center who received bleomycin, etoposide, and cisplatin (BEP) and to assess the menstrual and reproductive function of those who received conservative treatment. PATIENTS AND METHODS: Clinical information was abstracted from the medical record. Patients completed a detailed questionnaire about menstrual and reproductive function; those who did not return the questionnaire were interviewed by telephone. RESULTS: Twenty-six patients were identified as having been treated with BEP chemotherapy for pure ovarian dysgerminoma from January 1984 to January 1998. Their median age was 19.5 years (range, 7 to 32 years). Sixteen patients underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy. At a median follow-up time of 89 months, 25 (96%) of the 26 patients remained continuously disease-free. One patient apparently developed a second primary dysgerminoma in her remaining ovary after BEP and was clinically disease-free after further treatment. Of the 16 patients who underwent fertility-sparing surgery, one was lost to follow-up when she was pregnant, and one was still premenarchal. Of the remaining 14 patients, 10 (71%) maintained their normal menstrual function during and after chemotherapy, and 13 (93%) had returned to their prechemotherapy menstrual pattern at the time of the questionnaire. Five pregnancies have occurred thus far, and two patients have had difficulty conceiving. CONCLUSION: Most patients with metastatic dysgerminoma can expect cure with maintenance of normal reproductive function when treated with conservative surgery and BEP chemotherapy.

Adolescent↗