Biomedical subjects

J Fanning

Publications and source records attributed to J Fanning.

At least 19 recordsLinked to original sources

PubMed1992

Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma.

OBJECTIVE: To compare the survival with cisplatin, doxorubicin (Adriamycin), and cyclophosphamide versus that of cisplatin and cyclophosphamide in women with advanced epithelial ovarian cancer, to evaluate the effect of dose intensity, and to evaluate meta-analysis methodology. METHODS: Meta-analysis was done on 30 studies of 2060 women with stages III and IV epithelial ovarian cancer. All had 3-year survival data, adequate follow-up, no other chemotherapy, no radiation therapy, and had information for various prognostic variables (age, stage, grade, and residual disease). We used four different methods of meta-analysis: pooled published data and modified effect-size analyses of the entire group (30 studies), and pooled published data and effect-size analyses of the subset of five prospective randomized studies. RESULTS: Three-year survival for the entire group was 43% for cisplatin, doxorubicin, and cyclophosphamide versus 36% for cisplatin and cyclophosphamide; for the five prospective randomized studies, the rates were 46 and 35%, respectively. The survival advantage of cisplatin, doxorubicin, and cyclophosphamide was statistically significant when analyzed by the pooled published data and modified effect-size meta-analysis of the entire group and the pooled published data meta-analysis of the five prospective randomized studies. The effect-size meta-analysis of the five prospective studies did not reach statistical significance. Total dose intensity and doxorubicin dose intensity were not significantly associated with survival advantage in cisplatin, doxorubicin, and cyclophosphamide use. CONCLUSIONS: There seems to be a survival advantage to treatment with cisplatin, doxorubicin, and cyclophosphamide versus treatment with cisplatin and cyclophosphamide. We believe this to be due to the properties of multiagent chemotherapy (the addition of doxorubicin) rather than to increased dose intensity. In addition, we believe that physicians need to familiarize themselves with meta-analysis methodology.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Laser vaporization conization.

Laser vaporization conization is a modified technique for the diagnosis and treatment of cervical intraepithelial neoplasia. Two circles are marked on the cervix with the laser; the inner circle outlines the circumference of the conization specimen, while the outer one outlines an area 3 mm peripheral to all colposcopically abnormal tissue. The area between the circles is vaporized to 7 mm. This initial vaporization allows easier manipulation of the conization specimen. Laser conization is then performed. This technique is significantly easier to perform than laser excisional conization or combination excisional-vaporization conization and thus is ideal for teaching residents laser conization. Besides ease of performance, laser vaporization conization retains the advantages of laser vaporization and provides a specimen for pathologic review. In this study the median laser time was 14 minutes. There was minimal operative hemorrhaging, and only one patient (2%) developed a secondary cervical hemorrhage. A significant laser artifact was present in one case (2%). One case of invasive squamous cell cancer was diagnosed.

Adult↗

PubMed1991

Cervical implantation metastasis by endometrial adenocarcinoma.

A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment.

Adenocarcinoma↗

PubMed1991

Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery.

The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Development of lung metastases after curative intraperitoneal chemotherapy in a rat colon cancer model.

A model of colon peritoneal carcinomatosis was developed by injecting 5 x 10(7) viable tumor cells intraperitoneally into Fisher 344 rats. All 40 control rats developed bulky abdominal tumor with ascites and died of peritoneal carcinomatosis and bowel obstruction (median survival 5 weeks). One day after tumor implantation, treatment group rats received a single intraperitoneal injection of single agent or combination chemotherapy. The most active intraperitoneal single agents were 5-fluorouracil, cisplatin, and etoposide. The most active combination was 5-fluorouracil and cisplatin. Combination chemotherapy produced a significant increase in median, 10-week, and 20-week survival (vs control and single agent). Six of 11 (55%) rats treated with intraperitoneal combination chemotherapy dying between 10-20 weeks died of lung metastasis with cure of intraperitoneal tumor. The increased ability of intraperitoneal combination chemotherapy to cure intraperitoneal disease was offset by the development of lung metastasis.

Adenocarcinoma↗

PubMed1991

Prognostic significance of the extent of cervical involvement by endometrial cancer.

The prognostic significance of the extent of cervical involvement by endometrial cancer is impossible to determine from the literature because previous reports have included fractional dilatation and curettage for staging, preoperative radiotherapy, and surgical stage III and IV disease. Therefore, we reviewed and restaged according to the new FIGO system all patients with endometrial cancer from January 1981 to December 1989. Of 180 patients undergoing hysterectomy for endometrial cancer, 20 had surgical stage II disease. No patient received preoperative radiotherapy. None of 12 patients (0%) with stage IIA disease developed recurrence, while 5 of 8 (63%) with stage IIB disease recurred (P less than 0.01). All 5 recurrences were in extrapelvic sites. Endocervical stroma invasion appears to import a statistically significant worse prognosis than endometrial glandular involvement.

Adenocarcinoma↗

PubMed1991

Phase II trial of cisplatin, adriamycin, and etoposide for metastatic endometrial adenocarcinoma.

Twenty patients with metastatic or recurrent endometrial adenocarcinoma not amenable to surgery or radiation were treated with monthly cisplatin (20 mg/m2 x 3), etoposide (75 mg/m2 x 3), Adriamycin (40 mg/m2) (PAV) and Megace. Patient characteristics were as follows: grade 3 differentiation, 55%; papillary subtype, 15%; prior radiotherapy, 70%; prior chemotherapy, 10%; and prior hormonal therapy, 20%. Hematologic toxicity was significant but acceptable: WBC nadirs, 50%; platelet nadirs, 40%. There was no hematologic mortality. There was a 75% objective response rate and a 55% complete response rate with PAV. The median survival was 15+ months, the 2-year survival was 42%, and the 2-year progression-free survival was 20%. PAV appears to be an active combination with acceptable toxicity in the treatment of metastatic or recurrent endometrial cancer, and we believe that phase III evaluation is indicated.

Adenocarcinoma↗

PubMed1991

Serial CA 125 levels during chemotherapy for metastatic or recurrent endometrial cancer.

The purpose of this study was to evaluate the role of serial CA 125 in monitoring disease status during chemotherapy in women with metastatic or recurrent endometrial cancer. CA 125 was measured in 21 women receiving cisplatin, etoposide, and Adriamycin for a total of 275 courses of chemotherapy (median eight). Eight of ten patients had elevated pre-therapy CA 125 levels (median 233 U/mL). CA 125 became and/or remained negative in all 20 women with responding or stable disease and was elevated in all nine patients who relapsed. The median level at the time of relapse was 56 U/mL. Levels were elevated before clinical relapse in five of nine patients (56%). Serial CA 125 may aid in the management of women receiving chemotherapy for advanced or recurrent endometrial cancer.

Aged↗

PubMed1990

Immunotherapy of gynecologic malignancies.

Systemic Corynebacterium parvum and BCG have limited activity in gynecologic malignancies. Although intraperitoneal C. parvum is active, its toxicity is prohibitive. Intraperitoneal alpha-interferon is an active second line agent for minimal residual disease following combination chemotherapy. Intraperitoneal interferon trials are ongoing. Alpha-interferon is also active against lower genital tract condyloma acuminata. Sufficient numbers of patients have not been evaluated to determine the activity of interleukin-2(IL-2) in gynecologic malignancies. Radioisotope labeled monoclonal antibodies can image gynecologic malignancies and may have a future therapeutic role. The last decade has witnessed a substantial growth in immunotherapy and has demonstrated a role for biologic agents in cancer therapy. Continued improvement in biologic therapies should lead to major advances in gynecologic cancer diagnosis and therapy.

Female↗

PubMed1990

Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Female↗

PubMed1990

Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma.

From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy-three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis.

Adenocarcinoma↗

PubMed1990

Comparison of cisplatin and carboplatin cytotoxicity in human ovarian cancer cell lines using the MTT assay.

In this study, we compared the cytotoxicity of cisplatin and carboplatin against a panel of human ovarian cancer cell lines using the MTT assay, a rapid colorimetric test that can be used to evaluate the number of residual viable tumor cells following chemotherapy. The established human ovarian cancer cell line OVCAR-3 and the recently isolated and characterized A721, A90, A286, A1, and A121A cell lines were evaluated for chemosensitivity. Each cell line was treated separately with cisplatin and carboplatin at concentrations ranging from 500 to 0.16 micrograms/ml. Various chemotherapeutic exposure periods (1, 4, 24, and 48 hr) were tested to determine maximal efficacy. All cell lines were more susceptible to cisplatin than carboplatin at all drug concentrations and all exposure periods tested (P = 0.005). The overall median 50% inhibitory concentration (ID50) for cisplatin was 107 micrograms/ml compared with 490 micrograms/ml for carboplatin P = 0.005). For both cisplatin and carboplatin a 24-hr exposure was significantly more cytotoxic than a 1-hr exposure (P = 0.003 and P = 0.006, respectively). These in vitro results suggest that cisplatin is significantly more cytotoxic than carboplatin against human ovarian cancer cell lines and that cisplatin should not be replaced by carboplatin in the treatment of advanced epithelial ovarian cancer until randomized trials using maximum dosing of the cisplatin-containing regimen are performed.

Adult↗

PubMed1990

Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium.

Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary.

Adenocarcinoma↗

PubMed1990

DNA content as a prognostic factor in endometrial carcinoma.

Two hundred thirty-three cases of endometrial carcinoma were analyzed for DNA content using flow cytometry of cell nuclei extracted from archival paraffin blocks. The median follow-up time for the cases was 8.7 years. Aneuploidy, present in 18% of tumors overall, was associated with adverse histologic type, high grade, and depth of invasion in the uterus. Aneuploidy was not detected in low-grade carcinomas. A DNA index greater than 1.5 strongly predicted death from disease. For endometrial adenocarcinoma and papillary serous carcinoma, this finding appeared independent of stage or tumor grade. The percentage of cells in S phase or G2 + M of the cell cycle did not predict clinical outcome in diploid tumors. Application of DNA analysis to low-stage endometrial cancers of high grade or of papillary serous type may be useful for selecting a subgroup of patients for adjuvant therapy.

Adenocarcinoma↗

PubMed1989

Recurrent typhlitis. A disease resulting from aggressive chemotherapy.

Neutropenic typhlitis is a frequently fatal disease most commonly reported in leukemics. The authors have treated eight such patients over the last 18 months. All patients had abdominal pain and sepsis during chemotherapy-induced neutropenia. CT scanning was diagnostic in six patients thought to have typhlitis. Two patients were not diagnosed before exploratory laparotomy. The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however. One patient underwent an elective right hemicolectomy after a second episode, and typhlitis did not recur despite neutropenia associated with a subsequent course of chemotherapy. It is concluded that successful treatment of this disease hinges on: 1) early diagnosis provided by a high index of suspicion and the use of CT scanning, 2) nonoperative treatment for uncomplicated cases, and 3) elective right hemicolectomy to prevent recurrence.

Adolescent↗

PubMed1989

Endometrial adenocarcinoma histologic subtypes: clinical and pathologic profile.

All cases of endometrial adenocarcinoma treated at the Geisinger Medical Center from January 1970 to June 1980 were retrospectively reviewed in an attempt to elucidate the clinical and pathologic profiles of the various histologic subtypes. Complete clinical and pathologic data was available in 418 cases of stage I endometrial adenocarcinoma. The frequency of the histologic subtypes were adenocarcinoma 66%, adenoacanthoma 16%, adenosquamous 5%, papillary 8%, clear cell 3%, and secretory 2%. Absolute 5-year survival was adenocarcinoma 88%, adenoacanthoma 91%, adenosquamous 62%, papillary 63% (P less than 0.01), clear cell 43% (P less than 0.001), and secretory 89%. When comparing the clinical and pathologic profile of the various histologic subtypes, adenosquamous (52%, P less than 0.001) and clear cell (43%, P less than 0.05) were associated with the highest percentage of grade 3 differentiation. Adenosquamous (38%, P less than 0.05) and clear cell (36%) also had the highest percentage of deep myometrial invasion. Papillary subtype (46%, P less than 0.05) was associated with the highest percentage of nulliparity. There was no difference among the subtypes when comparing menopausal status, exogenous estrogen, obesity, hypertension, diabetes, or uterine size. In summary, (1) adenocarcinoma and adenoacanthoma are the most frequent subtypes; (2) adenosquamous, papillary, and clear cell have decreased 5-year survival; (3) the decreased 5-year survival in adenosquamous and clear cell subtypes appears to be associated with increased grade 3 differentiation and deep myometrial invasion while the poor prognosis associated with papillary subtype was not related to grade or myometrial invasion.

Adenocarcinoma↗

PubMed1989

Analysis of failure patterns in stage III endometrial carcinoma and therapeutic implications.

The poor outcome of certain patients with Stage III endometrial carcinoma has led some investigators to direct adjuvant therapy to the abdominal cavity. To better define failure patterns, a review of 126 patients with Stage III endometrial carcinoma treated at four institutions was performed. Seventy-four patients were diagnosed at surgery with pathologic Stage III disease, whereas 52 patients presented with clinical Stage III disease. Most patients received external beam irradiation to the pelvis with a variety of boost techniques. Site of disease, grade, depth of invasion, and pathology were examined for prognostic significance. Actuarial techniques were used to analyze survival and recurrences. For the 52 clinical Stage III patients, 5-year survival was 36%. The median survival of 20 patients who were treated with radiation therapy (RT) following biopsy was 9 months. Pelvic control was poor in these patients, with 16/18 evaluable patients failing locally. Thirty-two patients who underwent resection with adjunctive RT had a 5-year survival of 48%. Local failure occurred in 40% of patients, whereas 38% of patients had abdominal failure. Isolated abdominal failure was infrequent with 6% failing as isolated recurrence, and 16% failing as the only site of distant disease. For 74 pathologic Stage III patients, 5-year survival was 54%. Local failure resulted in 20% of patients, and isolated abdominal failure occurred in 7% of patients. The subset of patients with ovarian or tubal involvement included 42 patients, with a 5-year survival of 60%. Further analysis of this subset by grade and depth of myometrial penetration was found to be prognostically significant. Twenty-four patients who were Stage III because of parametrial or pelvic peritoneal involvement had a 5-year survival of 44%. Local control and survival is improved in Stage III patients treated with surgical resection. The high rate of distant metastases in both abdominal and extra-abdominal sites has significant therapeutic implications.

Adult↗

PubMed1989

Resolution of malignant small bowel obstruction after intraperitoneal etoposide therapy.

In the case we have reported, abdominal carcinomatosis with malignant small bowel obstruction (due to metastatic lung adenocarcinoma) developed despite ten cycles of cisplatinvinblastine and eight months of treatment with interferon and interleukin-2. Etoposide (VP-16) administered intraperitoneally as part of a phase I trial produced dramatic relief of the obstruction.

Abdominal Neoplasms↗