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Biomedical subjects

A Manetta

Publications and source records attributed to A Manetta.

At least 73 records · Page 4Linked to original sources

Benign and malignant pathology of the cervix, including screening.

This review focuses on the newly described and redefined benign and malignant lesions of the uterine cervix. The World Health Organization (WHO) classification of the cervix and the Bethesda system are discussed. In addition, the definition of early invasive squamous cell carcinoma is reviewed, and the diagnostic approach, natural history, and oncogenesis of pre-invasive and invasive squamous and glandular lesions are re-examined. The use of human papillomavirus (HPV) DNA detection and its association with cervical intraepithelial neoplasia (CIN) is briefly mentioned. Certain types of benign cervical lesions which mimic neoplasms, including atypical microglandular hyperplasia, and immature papillary metaplasia are mentioned. The unusual subtypes of cervical neoplasm, including villoglandular adenocarcinoma, small cell undifferentiated carcinoma, adenoid basal cell carcinoma, and adenoid cystic carcinoma are reviewed, with emphasis on differential histologic features, as the prognosis for those tumors may differ. Finally, immunohistochemical findings and tumor markers of cervical tumors are briefly mentioned.

Female↗

Comparison of adenocarcinoma and squamous cell carcinoma of the uterine cervix: a population-based epidemiologic study.

OBJECTIVE: Our objective was to compare epidemiologic and clinical characteristics of adenocarcinoma with those of squamous cell carcinoma of the cervix, with respect to risk by ethnic group, age at diagnosis, stage of disease at diagnosis, and survival. STUDY DESIGN: All data were obtained from the Cancer Surveillance Program of Orange County, California, from 1984 through 1989. A total of 152 cases of adenocarcinoma and 457 of squamous cell carcinoma of the uterine cervix were included. RESULTS: Adenocarcinoma of the cervix was diagnosed at a younger age and an earlier stage than squamous cell carcinoma. Hispanics have the highest risk for squamous cell carcinoma, whereas Asians have the highest risk for adenocarcinoma compared with whites. No differences were observed between the two histologic types in prognosis and survival. CONCLUSION: Differences between the two histologic types of cervix cancer were found in the age at diagnosis, the extent of disease, and the ethnic distribution. In spite of these differences, prognosis and survival were not affected by histologic type.

Adenocarcinoma↗

Radical hysterectomy in the elderly patient: analysis of morbidity.

OBJECTIVE: This study compares the perioperative morbidity and mortality following radical hysterectomy of patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA. STUDY DESIGN: A retrospective analysis of morbidity and mortality for the first 60 postoperative days was conducted. The study population of 45 women greater than 65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women less than 65 years treated similarly. RESULTS: In the elderly group, 31 of 45 and 12 of 15 were American Society of Anesthesologists Physical Status II and III respectively; 68/90 and 19/90 were American Society of Anesthesiologists status I and II in the younger age group (p = 0.001). Transfusions of greater than 2 units were required in 14% of the elderly and 35% of younger patients (p = 0.02). No statistical differences were observed between groups for other parameters examined. CONCLUSION: Age alone should not be a contraindication for radical hysterectomy in the elderly patient with American Society of Anesthesiologists Physical Status I to III.

Age Factors↗

Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy.

The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulae and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high-risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity.

Adenocarcinoma↗

Serum CA125 regression in epithelial ovarian cancer: correlation with reassessment findings and survival.

Findings at reassessment laparotomy and disease-free survival are reported for a group of patients with advanced-stage epithelial ovarian cancer who have had a complete clinical response to cytoreductive surgery and multiagent platinum-based chemotherapy. The predictive value of the number of chemotherapy cycles to achieve a serum CA125 of < 35 U/ml is compared to the predictive value of s, the rate of achieving a normal serum CA125. s is generated from an exponential regression model. This study suggests that s accurately predicts which patients have residual disease at reassessment laparotomy, who will be free of disease, and, of those in the latter group, who are at greatest risk to recur, as well as overall survival. If these observations are confirmed, physicians may base further therapeutic intervention on the basis of a calculated parameter following complete clinical response to first-line treatment rather than relying on findings at reassessment laparotomy.

Aged↗

Hypogastric artery aneurysm masquerading as an ovarian neoplasm.

Hypogastric artery aneurysm in women is rare. The case presented demonstrates how this lesion can easily mimic an ovarian neoplasm. The missed diagnosis can be catastrophic if the surgeon is unfamiliar with the retroperitoneal anatomy and is confronted with arterial hemorrhage. Hypogastric artery aneurysm should be included in the differential diagnosis of a pelvic mass in elderly women with atherosclerotic disease. The report reviews the literature on the presentation, diagnosis, and recommended treatments.

Aged↗

Trafficking of syngeneic murine lymphokine activated killer T cells following intraperitoneal administration in normal and tumor bearing mice.

Nongenetically restricted T cells may be important host effector cells in women with ovarian cancer receiving intraperitoneal (ip) IL-2 therapy. We developed an in vitro technique to produce murine lymphokine-activated killer T cells. Murine splenocytes were cultured in the presence of 1000 U/ml IL-2 for 10 to 15 days. Phenotypical analysis showed 95% of total cells to express the pan T phenotype Thy 1.2 and no NK cell phenotypes by Day 7 in culture. These cells were labeled with 51Cr and their trafficking pattern after ip administration into normal and M5067 tumor bearing mice was examined. Various organs and tissues were collected at different timepoints and monitored for radioactivity. Within 4 hr., about 60% of the counts were associated with the bowel, peritoneum, and omentum of both normal and tumor bearing mice. About 15% of counts were associated with the blood, lung, kidney, spleen, and liver of both normal and tumor bearing mice.

Animals↗

Immunotherapy of ovarian cancer. II. In vitro generation and characterization of lymphokine-activated killer T cells from the peripheral blood of recurrent ovarian cancer patients.

We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy.

Cell Division↗

Blocking factors (soluble membrane receptors) for tumor necrosis factor and lymphotoxin detected in ascites and released in short-term cultures obtained from ascites and solid tumors in women with gynecologic malignancy.

Studies were conducted to identify and establish the cell and tissue source of blocking factors (BF), materials that inhibit the bioactivity of human TNF and LT in vitro. Ascites and samples of solid tumors were collected from women with various gynecologic malignancies. Supernatants were collected from cultures of tumor and ascites cells after 24, 48, and 72 h. Cell-free ascites (CFA) and culture supernatants were tested for their ability to block human recombinant TNF and LT-induced lysis of L929 cells in vitro. Levels of soluble forms of the 55- and 75-kDa TNF/LT receptors were measured by ELISA assay in the same samples. CFA and culture supernatants contained TNF/LT blocking factors and high levels of one or both soluble 55- and 75-kDa TNF/LT membrane receptors. Levels of BF bioactivity and receptors appeared rapidly, peaked at 24 h, and declined thereafter. Soluble TNF/LT receptors may be the active BF in these samples, and tumor tissues and ascitic cells may be a source of these receptors in the ascites fluid of these patients.

Ascites↗

Gynecologic Oncology Group studies with ifosfamide.

The Gynecologic Oncology Group has conducted a series of phase II studies with ifosfamide and mesna since 1985. Previously untreated patients received ifosfamide 1.5 g/m2 intravenously daily for 5 days. Mesna was given intravenously every 4 hours three times daily at 20% of the daily ifosfamide dose. Because of the toxic effects observed in previously treated patients with ovarian cancer, the ifosfamide dose was reduced to 1.2 g/m2/d in patients with prior chemotherapy or radiotherapy. In epithelial ovarian cancer, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses. In patients with squamous carcinoma of the cervix, an 11.1% response rate (three of 27 patients) was observed in those who had received prior platinum therapy. In 51 previously untreated patients, the response rate was 15.7%. In nonsquamous cervical carcinomas, there were three partial responses among 25 patients (12%). An 8.6% response rate was observed among 23 patients with previously treated endometrial adenocarcinomas. In uterine sarcomas, response rates were 30.7% in mixed müllerian tumors, 17.2% in leiomyosarcomas, and 27.3% in endometrial stromal sarcomas. Patients with ovarian sarcomas responded in 27.8% of cases. Studies with ifosfamide combinations are currently under way by the Gynecologic Oncology Group.

Adenocarcinoma↗

Conservative surgical management of dysgerminoma concomitant with pregnancy.

Three cases of pure dysgerminoma concomitant with pregnancy were managed by conservative surgery and term delivery. One woman with advanced disease received chemotherapy for the last trimester. Tumor response, measured by normalization of the serum tumor markers CA 125 and lactic dehydrogenase, was confirmed by magnetic resonance imaging.

Adult↗

CA 125 regression: a model for epithelial ovarian cancer response.

The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method.

Adult↗

Radiation myelitis: a complication of concurrent cisplatin and 5-fluorouracil chemotherapy with extended field radiotherapy for carcinoma of the uterine cervix.

Radiation myelitis is a rare but serious complication of radiation therapy. The total dose of radiation to the spinal cord required to cause myelopathy is greater than 50 Gy when the treatment is administered in 25 or more fractions; however, recent evidence has suggested that the concurrent use of chemotherapy may decrease the tolerance of the spinal cord to radiation. This report describes a case of radiation myelitis in a patient after concomitant fluorouracil/cisplatin chemotherapy and extended field radiotherapy for stage IIA adenosquamous cell carcinoma of the uterine cervix metastatic to the para-aortic lymph nodes.

Adenocarcinoma↗

Does intraperitoneal CA-125 reflect disease status?

The relationship of serum CA-125 to intraperitoneal (IP) CA-125 was studied in 45 patients with a variety of gynecologic diseases including ovarian carcinoma. In 43 of 45 patients the IP level exceeded the serum level of CA-125. Paracentesis may dramatically alter both levels, thus mimicking surgical debulking. All IP levels of CA-125 measured at second-look coeliotomy for the ovarian cancer patients were within the normal range of IP CA-125 measured at surgery for benign disease. Therefore, intraperitoneal CA-125 is less sensitive than serum CA-125 in predicting intraperitoneal disease status. Likewise it cannot be used to predict the subgroup of ovarian cancer patients with negative second-look coeliotomy who are destined to develop a recurrence of disease.

Antigens, Tumor-Associated, Carbohydrate↗

Analysis of prognostic factors and survival in patients with ovarian cancer treated with second-line hexamethylmelamine (altretamine).

Hexamethylmelamine (altretamine, HMM) 260 mg/m2/day p.o. for 14 days followed by a 14-day drug-free interval was administered to 52 outpatients with advanced ovarian cancer who had previously been treated with chemotherapy. Prior to HMM, 92% (48/52) of these patients had received cisplatin and cyclophosphamide with or without doxorubicin. Two more patients received other cisplatin-based regimens. At the completion of HMM therapy, 15% (8/52) displayed no evidence of disease (NED). Of these eight patients, five are still alive 32 to 82 months after altretamine therapy (median follow-up of 46 months). At 41 months, one patient died of intercurrent illness with no clinical evidence of recurrence; the other two patients died of their disease at 21 and 31 months following HMM therapy. The median survival of the total group was 11 months: nine months for patients who did not respond to altretamine and 46+ months for patients with NED after altretamine (p less than 0.05). Intermittent oral administration of single-agent altretamine was well tolerated: eight patients reported moderate gastrointestinal symptoms, and only one patient reported severe gastrointestinal symptoms. Moderate neurologic toxicity was reported by five patients. No WBC fell below 2000 mm3 and platelet counts fell below 100,000 mm3 in only three patients; no patient experienced severe hematologic toxicity. In this series of patients, the overall response (15%) was comparable to or better than those reported for more toxic chemotherapeutic regimens. On the basis of these data and those reported by other investigators, HMM warrants consideration as a reasonable option in the management of recurrent or persistent ovarian cancer.

Altretamine↗

Simplified postoperative patient-controlled analgesia on a gynecologic oncology service.

Twenty-nine women who underwent various abdominal operations for gynecologic malignancies self-administered postoperative analgesia by means of disposable Travenol Infusors with Patient Control Modules. Administration of morphine sulfate at a rate of 1 mg per injection and a maximum of 10 mg per hour via patient-controlled analgesia was judged satisfactory by all 29 patients. The mean dose rate administered ranged from 1.2 to 1.5 mg per hour per day during the first 3 days postoperatively. No respiratory depression occurred and excessive sedation was reported by only 2 patients after the first 24 hr postoperatively. If further surgeries were required, more than 90% of these patients would prefer patient-controlled analgesia to intramuscular injections.

Adult↗

In vitro cytotoxicity of human recombinant tumor necrosis factor alpha in association with radiotherapy in a human ovarian carcinoma cell line.

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors.

Carcinoma↗