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A F Fuller

Publications and source records attributed to A F Fuller.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma, with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR-5 cell line were injected i.p. into 6- to 8-week-old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site-dependent and tumor cell survival was dose-dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor-bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

Animals↗
PubMed1996

Natural history of patients with pulmonary metastases from uterine cancer.

BACKGROUND: Endometrial cancer is the most common female genital cancer and approximately 90% of the cases are diagnosed while they are still confined to the uterus. However, the natural history and treated course after the development of pulmonary metastasis (PM) have not been studied systematically in a large series of patients. METHODS: Between 1962 and 1992, 100 patients (6%) with PM were identified by computerized search of the medical records from 1.665 patients admitted to our hospitals with the diagnosis of uterine cancer. The median age of the patients was 65.5 years (range: 42-87 yrs). The usual histologic types of the uterine neoplasms were 59 adenocarcinomas (59%), 21 sarcomas, and 14 adenosquamous carcinomas. Of the 83 patients with reported tumor grade, 11 had Grade 1 tumor, 12 Grade II, and 60 Grade III. RESULTS: Lung metastases were found at the time of diagnosis of the primary tumor in 22 patients. Hemoptysis was the first symptom of 3 of the 22; the majority had no respiratory symptoms. In the remaining 78 patients with PM appearing after primary therapy, the mean interval time between primary diagnosis and PM was 29.4 months, whereas between PM and death was 15.7 months. Of all patients with lung metastases, 75% did not survive 1 year; however 6% survived more than 5 years after diagnosis of metastatic disease. Patients with isolated PM had prolonged survival (36.1 mos, P=0.001), whether treated medically or with pulmonary resection. Progestin therapy was given to 39 patients, with complete response consisting of radiographic resolution of all disease in 6 patients (15%) and prolonged stabilization in an additional 5 (13%). The histologic grade of the primary tumor was predictive of clinical response to progestine therapy. CONCLUSIONS: Asymptomatic pulmonary metastases represent a common site of extra pelvic spread of disease. The majority of patients with PM (75%) do not survive 1 year. Low grade uterine tumors are more likely to respond to progestin therapy and do so for extended periods of time.

Adenocarcinoma↗
PubMed1996

Histologic transformation of benign endometriosis to early epithelial ovarian cancer.

Between 1975 and 1990, 79 patients with Stage I epithelial ovarian cancer were treated at Massachusetts General Hospital. Patients were identified from the tumor registry and medical records were retrospectively reviewed. Pathological slides were evaluated for the presence of endometriosis, specifically looking for malignancy arising in endometriosis. Evidence of endometriosis was found in 22 of the 79 cases (28%). In the 23 cases of endometrioid histology, 9 cases (39%) were associated with endometriosis and, in the 17 cases of clear cell tumors, 7 (41%) were associated with endometriosis. All 8 cases of mixed histology had clear cell and/or endometrioid components and 4 cases (50%) were associated with endometriosis. Endometrioid adenocarcinoma accounted for 41% of the tumors associated with endometriosis, clear cell carcinoma 31%, mixed (endometrioid and/or clear cell types) 18%, and other types 9%. Among the 22 patients with associated endometriosis, we found 7 carcinomas (32%) arising in endometriosis. In these 7 cases a spectrum of benign and atypical endometriosis with a transition to clear cell or endometrioid adenocarcinoma were identified. These premalignant changes were characterized by cytologic atypia and architectural proliferation. Endometriosis was frequently encountered among patients with Stage I epithelial ovarian cancer of endometrioid and clear cell histologies. Endometriosis may play a role in the pathogenesis of some early stage malignant ovarian epithelial neoplasms.

Adenocarcinoma, Clear Cell↗
PubMed1996

Clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy in stage III disease.

Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the surgical specimen compared with one (3%) in the papillary serous group (P = 0.002). Ten women (42%) with clear cell histology experienced a thromboembolic event during the course of treatment, compared to six (18%) in the papillary serous group (P = 0.05). In the group with clear cell histology, overall, 70% of women had progressive disease. Fifty-two percent experienced clinical progression while receiving platinum-based chemotherapy. In addition, four patients were found to have progressive disease at second-look laparotomy. Only two patients had a pathologic complete response. In the group with papillary serous histology, 29% overall had progressive disease while on chemotherapy (P = 0.005). The median survival for the women with clear cell histology was 12 months compared to 22 months for those with papillary serous (P = 0.02). For women with clear cell histology, univariate analysis was used to evaluate prognostic factors. Age less than 50 was a poor prognostic factor (P = 0.045). The presence of endometriosis, thromboembolic event, or optimal cytoreduction were not prognostic factors (P = 0.67, P = 0.34, P = 0.39). Patients with advanced clear cell ovarian cancer have a poor response to conventional platinum-based chemotherapy and overall prognosis is poor.

Adenocarcinoma, Clear Cell↗
PubMed1996

Squamous cell carcinoma of the endometrium: a report of eight cases and a review of the literature.

BACKGROUND: Endometrial squamous cell carcinoma is extremely rare, with only 56 cases reported in the literature. METHODS: Six cases of endometrial squamous cell carcinoma were found in a review of 1182 cases of uterine corpus cancer treated at the Massachusetts General Hospital from 1975 to 1993. Two additional cases were seen in pathological consultation. The clinicopathological features of these 8 cases and the 56 reported cases were analyzed. RESULTS: The average age of the patients was 67 years; almost all of them were postmenopausal. The most frequent presenting symptom was vaginal bleeding. Chronic pyometra and nulliparity were predisposing factors. The average duration of symptoms before diagnosis was 11.5 months. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was the primary treatment in 58 patients. Eighty percent of the patients with Stage I tumors survived; the median follow-up time was 32 months. The survival rate for patients with Stage III tumors was only 20%, and all 6 patients with Stage IV disease died. CONCLUSIONS: The preoperative diagnosis of endometrial squamous cell carcinoma may be difficult, since curettage specimens may show only highly differentiated squamous epithelium. The strong relationship between tumor stage and survival suggests that early diagnosis and treatment are imperative.

Aged↗
PubMed1996

The effect of postsurgical therapy on stage III endometrial carcinoma.

The records of 86 pathologic stage III endometrial carcinoma patients treated at Massachusetts General Hospital between 1974 and 1992 were retrospectively reviewed to identify predictors of poor outcome and to determine the effect of postsurgical therapy on recurrence and survival. Patients underwent TAH/BSO with selective lymphadenectomy and peritoneal washings. Cases prior to 1988 were retrospectively restaged using the FIGO surgical staging criteria. Postoperatively, patients received individualized regimens of EBRT (external beam radiotherapy), brachytherapy, and cytotoxic or hormonal chemotherapy. The 5-year survival and 5-year disease-free survival (DFS) for all patients were 54 and 44%, respectively. Forty-two percent of stage IIIA/B patients recurred in a median time of 14 months. Fifty-four percent of stage IIIC patients recurred in a median time of 16 months. Of patients who recurred, 90% stage IIIA/B and 71% stage IIIC patients recurred at extrapelvic sites. Age greater than 70, high-grade lesions, and fallopian tube metastases were predictive of poor outcome in stage IIIA/B by multivariate analysis. Vascular invasion was the only poor prognostic factor identified by multivariate analysis in stage IIIC disease. No benefit from pelvic EBRT in stage IIIA/B could be identified. Stage IIIC patients had increased DFS and a trend for increased survival with pelvic EBRT. Chemotherapy did not improve survival in either group.

Adult↗
PubMed1996

Postoperative management of patients with stage Ib endometrial carcinoma.

Between 1980 and 1990, 124 patients with Stage Ib endometrioid adenocarcinoma of the endometrium were treated at Massachusetts General Hospital (MGH). Patients were identified from the tumor registry and medical records were retrospectively reviewed. Of the 124 patients, four (3%) developed a recurrence. Eighty-six patients had grade 1 tumors, 32 grade 2 and 6 grade 3. Recurrences developed in two (2%) of the grade 1 tumors, one (3%) of the grade 2, and one (17%) of the grade 3. Of the 86 patients with grade 1 carcinomas, 58 received no adjuvant radiation, 25 received vaginal vault brachytherapy and 3 whole pelvic radiation (WPR). Of the 32 patients with grade 2 tumors, 13 received no adjuvant therapy, 10 vaginal brachytherapy, and 9 WPR. Of the six patients with grade 3 tumors, one received no adjuvant therapy, two vaginal brachytherapy, and three WPR. Of the four women that relapsed, only the patient with grade 3 tumor had been treated with adjuvant radiation (WPR). Three of the four patients recurred at the vaginal vault and all three were salvaged. Stage Ib, grade 1 and 2, endometrioid adenocarcinomas have a good prognosis and adjuvant radiotherapy is not clearly beneficial.

Adenocarcinoma↗
PubMed1995

Malignant mixed müllerian tumors of the ovary: experience with surgical cytoreduction and combination chemotherapy.

BACKGROUND: The role of surgical cytoreduction and combination chemotherapy for malignant mixed müllerian tumors (MMMT) of the ovary was evaluated. METHODS: A retrospective review of 27 women with ovarian MMMT treated from 1980 to 1990 was performed. RESULTS: The International Federation of Gynecology and Obstetrics stages for the 27 women were 1 Stage I, 3 Stage II, 17 Stage III, and 6 Stage IV. Only 10 of the 23 patients with Stage III or IV disease were cytoreduced optimally. With respect to postoperative therapy, 3 women received no treatment, 6 were treated with whole abdomen radiotherapy, 1 received melphalan, and 17 received chemotherapy incorporating a platinum agent (3), doxorubicin (4), or both (10). The significant prognostic factors were stage (P < 0.001) and, for women with Stage III or IV disease, the feasibility of cytoreductive surgery (P = 0.03). The four patients in Stages I or II remained disease free after an interval of at least 5 years. The median and 5-year survival rates for patients with Stages III or IV disease was 18 months and 8%, respectively. Patients in Stage III or IV for whom optimal cytoreduction was not possible had a 2-year survival of 14%, whereas optimal cytoreduction was associated with a 52% 2-year survival. Median survival for the 14 women with Stage III or IV ovarian MMMT treated with combination chemotherapy was 25 months and nine women achieved progression free intervals of greater than 18 months. CONCLUSIONS: Aggressive surgical cytoreduction followed by combination chemotherapy may result in improved progression free intervals for women with advanced ovarian MMMT. However, a major improvement in prognosis for this rare malignancy has not yet been achieved.

Aged↗
PubMed1995

Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases.

Between 1975 and 1989, 896 patients were treated for endometrial carcinoma at the Massachusetts General Hospital. Thirty patients were identified from the tumor registry as having uterine papillary serous carcinomas. The survival for all patients and for groups of patients stratified on clinical and pathological parameters was examined in the Kaplan-Meier survival curves. Curves for the different strata were compared using the logrank test. The 5-year survival for the 30 patients was 30% +/- 9%. Patients with surgical stage I and II tumors had a 5-year survival rate of 79% +/- 14% compared to 25% +/- 10% in patients with stage III and IV tumors (P = 0.02). Clinical stage, depth of myometrial invasion, lymph-vascular space invasion, tumor grade, and DNA aneuploidy were not found to significantly impact on survival. However, a survival advantage was seen in patients diagnosed with early surgical stage tumors, reinforcing the need for thorough staging at the time of laparotomy.

Aged↗
PubMed1994

Surgical stage IV endometrial carcinoma: a study of 47 cases.

Between 1976 and 1991, 47 patients with surgical Stage IV endometrial carcinoma were treated. Patients were identified from the tumor registry and charts were retrospectively reviewed. Surgical curves using the Kaplan-Meier product-limit method and Cox regression analysis were used to identify independent prognostic factors. Overall, median survival was only 12 months. Using univariate analysis there was no statistically significant difference in survival between age (P = 0.41), histology (P = 0.54), grade (P = 0.91), disease site (P = 0.32), or clinical stage (P = 0.87). In patients whose disease was surgically cytoreduced, the median survival was 18 months compared to 8 months in those who did not undergo surgery (P = 0.0001). Evaluation of other treatment modalities by univariate analysis revealed improved survival in those patients who received cyclophosphamide, doxorubicin, and cisplatin (P = 0.0007), decreased survival in those who received radiation therapy compared to surgery (P = 0.023), and no statistically significant difference in survival with progestins. By multivariate analysis successful cytoreduction was the only statistically significant prognostic variable (P = 0.04). This 15-year retrospective review confirms that prognosis for women with Stage IV endometrial cancer is extremely poor. However, if hysterectomy with cytoreduction is feasible, surgery should be performed because survival may be improved.

Aged↗
PubMed1994

Prognostic significance of DNA content in epithelial ovarian cancer.

The prognostic significance of cellular DNA content of epithelial ovarian cancer as determined by flow-cytometric analysis of paraffin-embedded tumor blocks was investigated in 87 patients. Seventy-five percent of tumors were DNA aneuploid and 25% were DNA diploid. The survival at median follow-up for patients with DNA diploid tumors (68%) was significantly longer than for DNA aneuploid tumors (49%; P = 0.003). The other prognostic factors which significantly affected survival were stage (P < 0.0001), tumor grade (P < 0.006), and residual disease at completion of initial surgery (P = 0.0005). When patients were separated into low-stage and advanced-stage disease, DNA content was a significant prognostic variable for survival in Stage I and II patients (P = 0.05). In Stage III and IV patients, DNA content had no independent prognostic significance. There were 33 patients who underwent second-look surgery. Seven of 15 patients (47%) with negative second-look surgery were DNA aneuploid, whereas 17 of 18 patients (94%) with positive second-look surgery were DNA aneuploid. Therefore, there was a much higher likelihood of positive second-look in the DNA aneuploid group (17/24) compared to the DNA diploid group (1/9) (P = 0.003). In addition for those patients with negative second-look surgery, none (0/8) of the DNA diploid tumors recurred; however, 3 of 7 (43%) of the DNA aneuploid tumors recurred and died. Cox proportional/hazards analysis showed that DNA content is an independent prognostic factor for survival in epithelial ovarian cancer. Aneuploid DNA content in ovarian tumors is also correlated with more aggressive biologic behavior, and therefore, a worse clinical course.

Adult↗
PubMed1994

Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms.

OBJECTIVE: To determine whether rupture of malignant ovarian epithelial tumors at the time of operation influences the patient's overall prognosis. METHODS: Between 1975 and 1990, 79 patients with stage I invasive epithelial ovarian cancer were treated at Massachusetts General Hospital. Patients were identified from the tumor registry, and charts were reviewed retrospectively. In 71 of the 79 cases, pathologic slides were evaluated. Of the 79 patients, 36 had stage Ia tumors, 20 stage Ic secondary to intraoperative rupture (Ic-rupture), and 17 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-other). Survival analysis was performed to compare the three groups of patients. RESULTS: There were four recurrences and deaths among the 20 women with stage Ic-rupture tumors (20%), compared to one (3%) among the 36 women with stage Ia. The recurrence-free survival at the median follow-up time for the two groups was 97 +/- 3 and 78 +/- 10 months, respectively (P = .03); overall survival was 97 +/- 3 and 73 +/- 12 months (P = .04). There were two recurrences (12%) and one death (6%) among the 17 women with stage Ic-other, giving recurrence-free and overall survivals of 88 +/- 8 and 94 +/- 6 months, respectively. The survival experience of this last group was not significantly different from that in the Ic-rupture group (P = .2). The hazard ratios for overall survival associated with stage Ic-rupture and each potential confounder, except for bloating, exceeded 6.5, with P < or = .10. All deaths occurred in the 28 patients with grade 2 or 3 tumors. Even in this smaller group, the hazard ratio for stage Ic-rupture was 6.8 (P = .09). CONCLUSION: Intraoperative rupture of malignant epithelial ovarian neoplasms may worsen the prognosis of patients with stage I ovarian cancer.

Ascitic Fluid↗
PubMed1993

Uterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence.

This study was undertaken to examine the incidence and conditions under which lymph node metastases are present and patterns of recurrence in women with uterine leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), excluding malignant mixed mesodermal tumors. From 1981 through 1991, 21 women with LMS and 10 women with ESS were treated. Retroperitoneal lymph node dissections were performed in 15 women with LMS and 7 women with ESS. In the women with LMS, 4/15 (26.7%) had lymph node metastases; in each there was disseminated intra-abdominal disease. In the 7 women with ESS, there were no lymph node metastases present. Ten women (47%) with LMS developed recurrences, and 3 (14%) had persistent disease. In the 10 women with ESS, 3 (30%) had recurrences, and 1 (10%) had persistent disease. In total, recurrences involved the lung in 84% of cases. Of the 13 women with recurrences, 7 had undergone lymph node sampling, and all were negative; 4 additional women had no evidence of adenopathy on abdominal-pelvic CT scan. Lymph node metastases were found only with extrauterine disease, and in all of these cases there was rapid progression of the sarcoma. Women without extrauterine disease did not have lymph node metastases detected; however, there was still a high rate (40%) of distant failure. Knowledge of lymph node status had minimal impact on the clinical management of women with uterine LMS and ESS.

Adult↗
PubMed1993

Epithelial ovarian tumors of borderline malignancy: long-term follow-up.

Thirty-nine patients underwent primary surgery for epithelial ovarian tumors of low malignant potential at the Massachusetts General Hospital between 1970 and 1980. Eighty-five percent of patients were found to have Stage I disease and 15% were found to have Stage III disease. Fifty-four percent of patients had a tumor with serous histology, 39% had a tumor with mucinous histology, and the remainder of patients had tumors with an endometrioid or mixed-cell type. Second malignancies and benign ovarian tumors were frequently found concomitantly with the borderline tumors or in follow-up. Gastrointestinal and endometrial adenocarcinomas were the most common second malignancies and were frequently found associated with a borderline tumor of serous histology. Follow-up was available in all 39 patients (100%). Mean time of follow-up was 11.8 years. Sixty-nine percent of patients are clinically without evidence of disease with a mean follow-up of 14.7 years, 23% died of other causes, 5% died of disease, and 3% died with disease and sepsis. All patients dying with disease did so within 7.3 years of their primary surgery. Seven patients underwent conservative surgery, defined as preservation of some ovarian tissue. Six of 7 patients are clinically free of disease with a mean follow-up of 14.6 years; 1 patient died of other causes. No patients treated conservatively had a recurrence of their disease.

Adenocarcinoma↗
PubMed1993

Primary leiomyosarcoma of the fallopian tube.

Primary leiomyosarcoma of the fallopian tube is an extremely uncommon neoplasm. We report a 39-year-old premenopausal woman with leiomyosarcoma confined to the right fallopian tube, who is alive without evidence of disease 2 years after surgical resection followed by adjuvant doxorubicin and cisplatin chemotherapy. An accompanying literature review indicates that the clinical signs and symptoms of fallopian tube sarcomas are usually nonspecific and include lower abdominal pain and pelvic pressure. The age at diagnosis varies from 21 to 70 years, with a median of 47 years. Prognosis is poor, however, several longterm survivors have been reported. The primary treatment remains surgical excision, although adjunctive chemotherapy or radiation may be of some benefit.

Adult↗
PubMed1991

Stage IE primary malignant lymphomas of the uterine cervix.

The experience of the authors with primary non-Hodgkin's lymphoma of the uterine cervix from 1980 to 1986 included five Ann Arbor Stage IE cases successfully managed by meticulous staging and radiation therapy. The clinicopathologic features of the patients are described and compared with 38 previously reported Stage IE cases. When all 43 patients were evaluated, the median age was 40 years of age (range, 20 to 80 years of age) and 77% were premenopausal. Most patients (74%) reported abnormal vaginal bleeding, although approximately 20% were asymptomatic. The primary cervical tumors were typically of large size, with half exceeding 4 cm in diameter. Using the International Federation of Gynecology and Obstetrics (FIGO) system for staging cervical cancer, stage distribution was 44% Stage I, 42% Stage II, 12% Stage III, and 2% Stage IV. Histologically, approximately 70% were of the diffuse, large cell type (Working Formulation). External beam radiation therapy supplemented by brachytherapy or hysterectomy was used for 76% of the patients reviewed. There was only one treatment failure among the 28 patients whose treatment included radiation and whose cases were followed for at least 2 years. This experience and a review of the literature indicate that most cases of primary lymphoma of the uterine cervix are Ann Arbor Stage IE, and can be cured with traditional combinations of surgery and radiation therapy after careful evaluation.

Aged↗