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Biomedical subjects

B A Goff

Publications and source records attributed to B A Goff.

At least 55 records · Page 3Linked to original sources

Uterine papillary serous carcinoma: patterns of metastatic spread.

Uterine papillary serous carcinoma (UPSC) is a distinct histologic type of endometrial cancer which is associated with a high relapse rate and poor prognosis. Between 1983 and 1993, 50 patients with UPSC of the endometrium were surgically staged. Thirty-three patients had pure UPSC and 17 had UPSC admixed with other histologies. Extrauterine disease was found in 36 women (72%). Lymph node metastases were present in 36% of women without myometrial invasion, 50% with inner one-half invasion, and 40% with outer one-half invasion. Similarly, the presence of intraperitoneal disease or positive washings did not correlate with increasing myometrial invasion. Grade and histology (mixed vs pure) were also not predictive of extrauterine disease. Patients with lymphatic/vascular space invasion (LVSI) were more likely to have extrauterine disease (85%); however, even without LVSI the incidence of extrauterine disease was 58% (P = 0.05). Unlike endometrioid adenocarcinomas, grade and depth of myometrial invasion were not significant predictors for extrauterine disease. This study reinforces the need for complete surgical staging in all patients with UPSC regardless of depth of invasion.

Aged↗

Photoimmunotherapy and biodistribution with an OC125-chlorin immunoconjugate in an in vivo murine ovarian cancer model.

Photodynamic therapy (PDT) is an experimental approach to the treatment of neoplasms in which photosensitisers (PSs) accumulated in malignant tissues are photoactivated with appropriate wavelengths of light. The target specificity of PSs may be improved by linking them with carrier macromolecules such as monoclonal antibodies (MAbs). OC125 is a murine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo studies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovarian cancer cell line NIH:OVCAR3. Six weeks after injection, when the animals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For both the IC and free PS, peak tumour concentrations were reached at 24 h; however, the absolute concentrations for the IC were always higher (2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h for the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for skin and 3.5 for intestine. Evaluation of viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dose-dependent relationship with fluence and IC concentration. However, there was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells was also significantly reduced and there were no treatment-related deaths. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control malignant disease yet maintain acceptable toxicity in vivo.

Animals↗

Large loop excision of the transformation zone in patients with exocervical squamous intraepithelial lesions.

This study was undertaken to determine factors influencing the success of loop excisions. One hundred twenty-seven women with exocervical intraepithelial lesions underwent large loop excision of the transformation zone (LLETZ); 102 returned for evaluation at 3 months. The pretreatment biopsies were low grade squamous intraepithelial lesions (LGSIL) in 37 cases and high grade squamous intraepithelial lesions (HGSIL) in 90. For the 37 women with LGSIL, the LLETZ specimen revealed no residual SIL in 13 (35%), LGSIL in 16 (43%), and HGSIL in 8 (22%). For the 90 women with HGSIL on pretreatment biopsy, 17 (19%) had no SIL, 10 (11%) had LGSIL, and 63 (70%) had HGSIL. Of the 102 women who returned for reevaluation, colposcopy was satisfactory in 89. There were 9 failures and all of these occurred in women with HGSIL in the LLETZ specimen. In the 17 women with involved margins there were 6 failures (35%); in the 85 women with uninvolved margins there were 3 failures (4%) (p = 0.005). The success of loop excisions is influenced by the grade of intraepithelial neoplasia and status of the margins of the LLETZ specimen.

Adenocarcinoma↗

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↗

Pseudomyxoma peritonei: a review of 23 cases.

OBJECTIVE: To review the experience at the Massachusetts General and Brigham and Women's Hospitals with 23 women treated for pseudomyxoma peritonei between 1961 and 1991. METHODS: Patients were identified retrospectively from the tumor registry at the Massachusetts General and Brigham and Women's Hospitals, and all charts were reviewed. The median follow-up interval was 2.5 years (range 3 months to 31 years). RESULTS: The mean age at diagnosis was 58 years (range 26-76). Pseudomyxoma peritonei was found in association with ten (44%) ovarian tumors of borderline malignancy, nine (39%) ovarian cystadenocarcinomas, and four (17%) appendiceal cystadenocarcinomas. Three patients had synchronous tumors in the ovary and appendix. All patients underwent surgical staging and cytoreduction. Eleven patients received postoperative therapy and, of these, nine developed a recurrence; 12 patients received no further therapy and, of these, three developed a recurrence. However, these groups were not pathologically comparable. With respect to survival, of the ten patients with borderline malignancies, seven had no evidence of disease, one was alive with disease, and two died of disease. For the nine patients with ovarian cystadenocarcinomas, three had no evidence of disease, one was alive with disease, and five died of disease (median time to death 18 months). For the four patients with appendiceal carcinomas, two had no disease, one was alive with disease, and one died with disease. Among all 23 patients, 12 (52%) developed a recurrence, with a range of time to first recurrence of 3 months to 19 years. Eight women required at least one additional laparotomy because of accumulation of gelatinous material. CONCLUSIONS: Although pseudomyxoma peritonei is associated with borderline and well-differentiated tumors, recurrence is common and the prognosis after recurrence is guarded. Involvement of the appendix is common; therefore, appendectomy is indicated when pseudomyxoma is encountered. To date, surgery has been the only effective therapy for this disease, and adjuvant therapy has not been shown conclusively to be of benefit.

Adult↗

Human papillomavirus typing in patients with Papanicolaou smears showing squamous atypia.

Three hundred sixty consecutive patients followed at the Massachusetts General Hospital Colposcopy Clinic had HPV typing performed from exfoliated cervical cells by a commercially available dot blot hybridization assay. This assay tests for three groups of HPV types: 6/11, 16/18, and 31/33/35. Of this group, 171 patients were referred because of a Papanicolaou (Pap) smear showing squamous atypia. Of the 171 patients referred for squamous atypia, 17 (10%) had histologic evidence of CIN. Thirty-three of the 171 (19%) had detectable HPV DNA, and 28 of the 33 had high-risk HPV types (16/18, 31/33/35). Of the 17 women with CIN, only 6 (35%) had high-risk types and 11 (65%) had no HPV DNA detected. Of the 28 women with atypia and high-risk HPV types, only 6 (21%) had CIN. This study demonstrates that commercially available HPV typing when used in patients with Pap smears showing squamous atypia is not clinically useful in identifying patients for colposcopic referral.

Carcinoma in Situ↗

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↗

Small chest-tube drainage followed by bleomycin sclerosis for malignant pleural effusions.

OBJECTIVE: To review our experience with bleomycin sclerotherapy as treatment of pleural effusions due to gynecologic malignancies. METHODS: Twenty-one women with histologically documented malignant effusions (16 ovarian carcinoma, three uterine sarcoma, and two cervical cancer) were treated with small flexible chest-tube drainage followed by intrapleural bleomycin sclerotherapy (60 units). RESULTS: After placement of the chest tube, suction was required for a median of 5 days (range 3-12) before output was low enough (less than 100 mL/24 hours) to instill bleomycin. Among 24 treated effusions, there was a 71% overall response rate, including ten complete responses (42%) and seven partial responses (29%); seven effusions (29%) did not respond to therapy. Six of the seven patients whose effusions did not respond to bleomycin died of disease within 2 months of attempted sclerotherapy. Fever was the most common side effect, occurring in 13 of 21 patients (62%) following instillation of bleomycin. Pain during sclerosis was reported by only two patients. CONCLUSIONS: Bleomycin sclerotherapy after small flexible chest-tube drainage of malignant pleural effusions is an effective technique, with minimal adverse reactions, for controlling effusions that develop in women with gynecologic malignancies.

Bleomycin↗

Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs.

Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer. The goal of this study was to evaluate the effect of PDT using topical ALA on normal guinea pig (g.p.) skin and g.p. skin in which the stratum corneum was removed by being tape-stripped (TS). Evaluation consisted of gross examination, PpIX fluorescence detection, reflectance spectroscopy, and histology. There was no effect from the application of light or ALA alone. Normal non-TS g.p. skin treated with ALA and light was unaffected unless high light and ALA doses were used. Skin from which the stratum corneum was removed was highly sensitive to treatment with ALA and light: 24 h after treatment, the epidermis showed full thickness necrosis, followed by complete repair within 7 d. Time-dependent fluorescence excitation and emission spectra were determined to characterize the chromophore and to demonstrate a build-up of the porphyrin in the skin. These data support the view that PDT with topical ALA is a promising approach for the treatment of epidermal cutaneous disorders.

Administration, Topical↗

Adenocarcinoma in situ of the uterine cervix.

OBJECTIVE: To assess the diagnostic accuracy of cervical conization in women with adenocarcinoma in situ and to determine whether a select group of women could be managed by conization alone without hysterectomy. METHODS: We retrospectively reviewed 40 cases of cervical adenocarcinoma in situ diagnosed on cervical conization. RESULTS: Cervical conization revealed adenocarcinoma in situ alone in 15 women. Twenty-five women had adenocarcinoma in situ coexisting with squamous dysplasia (23) or microinvasive squamous cell carcinoma (two). Twenty-two women underwent hysterectomy after cone biopsy. Adenocarcinoma in situ was detected in the hysterectomy specimen in one of 12 women with uninvolved cone margins, versus seven of ten women with involved margins (P = .006); two of these seven women also had foci of invasive adenocarcinoma in the hysterectomy specimen. Conization was the only treatment for 18 selected women with adenocarcinoma in situ and uninvolved margins; all were relapse-free after a median interval of 3 years (range 1.5-5). CONCLUSIONS: Women with cervical adenocarcinoma in situ diagnosed by conization who have positive margins are at high risk of residual adenocarcinoma in situ and moderate risk of occult invasive adenocarcinoma; expectant management is not warranted. However, a cone biopsy with uninvolved margins can reliably guide subsequent therapy. Selected young women who desire preservation of fertility and have uninvolved margins probably can be managed by conization alone, but further study is required to establish the safety of this approach.

Adenocarcinoma↗

Post-hysterectomy carcinoma of the fallopian tube mimicking a vesicovaginal fistula.

A 49-year-old woman presented with a profuse watery vaginal discharge 16 years after a vaginal hysterectomy. Pelvic examination revealed clear fluid leaking from the vaginal apex. Cytologic evaluation of the draining fluid was normal, as was a biopsy of the vaginal apex. A vesicovaginal fistula was suspected. Intravenous pyelogram and cystogram did not reveal communication of the urinary tract with the fistula. Injection of radiopaque dye through the fistula tract demonstrated a 5-7-cm enclosed cystic space with a 4-cm pedunculated mass within the cyst lumen. Exploratory surgery revealed fallopian tube carcinoma involving the right tube. The tumor mass was completely excised, and there was no evidence of spread beyond the encapsulated cystic fallopian tube. The woman was treated with six cycles of cisplatin combination chemotherapy, and after 5 years remains free of disease.

Adenocarcinoma↗

Endocervical glandular atypia in Papanicolaou smears.

The importance of endocervical glandular atypia in a cervicovaginal Papanicolaou smear has not been fully investigated. Between July 1988 and June 1989, 21,930 cervicovaginal smears were reviewed by the Massachusetts General Hospital Cytopathology Laboratory. One hundred smears with endocervical atypia were identified, an incidence of 0.46%. Follow-up was available on 63 cases: Seven had negative follow-up smears for at least 2 years, 15 had negative biopsies, seven had endocervical polyps, two had endometrial hyperplasia, eight had mild dysplasia, five had moderate dysplasia, six had severe dysplasia, six had squamous carcinoma in situ, five had adenocarcinoma in situ, and two had invasive adenocarcinoma. Twelve women's smears showed endocervical atypia with features suggestive of reactive atypia; three of these had dysplasia. Twenty-six (41%) of the Papanicolaou smears with endocervical atypia had coexisting squamous atypia or dysplasia. We conclude that endocervical atypia may be associated with substantial cervical disease in as many as half of cases.

Adult↗

Photoimmunotherapy of human ovarian carcinoma cells ex vivo.

Photodynamic therapy is a relatively new and potentially selective experimental approach to the treatment of malignant neoplasms. Its inherent dual selectivity is reinforced by the use of photosensitizer-monoclonal antibody conjugates. The goal of this study was to evaluate the phototoxicity and selectivity of an immunoconjugate (IC) synthesized from a chlorin derivative chlorin e6-monoethylenediamine monoamide (CMA) as the photosensitizer and an anti-ovarian carcinoma monoclonal antibody OC125. Binding efficiency and specificity of the IC were determined by enzyme-linked immunosorbent assay, and specific covalent linkage of the monoclonal antibody to the photosensitizer was demonstrated by fluorescence and electrophoresis. Phototoxicity was tested against ascites or pleural fluid cells from 15 patients with ovarian and nonovarian cancers. Tumor cells from the fluid were treated with the IC at 3 microM equivalent CMA concentration and irradiated at 654 nm (lambda max CMA in IC) at 25 J/cm2 from an argon ion-pumped dye laser. Phototoxic efficacy was assayed by [3H]thymidine incorporation. Ovarian cancer cells exhibited high cytotoxicity with [3H]thymidine incorporation of 2.4 +/- 2.2%, while nonovarian cancer cells under identical conditions exhibited none to reduced cytotoxicity with [3H]thymidine incorporation of 70 +/- 54%. Using a Wilcoxon test, there was a statistically significant difference between these two groups (P less than 0.001). Dose-response curves revealed reciprocity in photosensitizer concentration and fluence. These results demonstrate that photoimmunoconjugates retain significant antigen binding specificity and affinity, are effective in the selective photochemical eradication of target cells, and merit further evaluation as photochemotherapeutic agents.

Antibodies, Monoclonal↗

Combination chemotherapy in advanced adenocarcinoma of the fallopian tube.

Advanced adenocarcinoma of the fallopian tube has a poor prognosis, with 5-year survival rates commonly less than 20%. Since 1980, we have managed 12 patients with disseminated tumor with combination chemotherapy following surgical cytoreduction. Analogous to the International Federation of Gynecology and Obstetrics staging of ovarian carcinoma, 3 patients were classified in Stage II, 8 in Stage III, and 1 in Stage IV. Ten patients received cisplatin-containing regimens. The 3 Stage II patients, without measurable disease after primary surgery, had an indeterminate response to chemotherapy. In Stages III-IV there were 4 complete responses (3 confirmed by second-look laparotomy) and 2 partial responses, for an overall response rate of 67%. Disease progressed in 2 patients and was stable in 1 patient. After median follow-up of 3.5 years, 4 of the Stage III-IV patients have no evidence of disease, 1 is alive with disease, and 4 are dead.

Adenocarcinoma↗

Assessment of depth of myometrial invasion in endometrial adenocarcinoma.

Depth of myometrial invasion in stage I adenocarcinoma of the endometrium is recognized as a prognostic factor for lymph node metastasis and overall survival. To determine if depth of myometrial invasion estimated by gross examination correlated with final histologic depth of invasion, we retrospectively reviewed all cases of surgical stage I endometrial adenocarcinoma treated at our institution between July 1985 and July 1988. Of the 113 evaluable patients, 63 had grade 1 lesions, 37 grade 2 lesions, and 13 grade 3 lesions. The depth of invasion was accurately determined by gross examination in 55 of 63 (87.3%) grade 1 lesions, 24 of 37 (64.9%) grade 2 lesions, and only 4 of 13 (30.8%) grade 3 lesions. Thus, gross examination of fresh tissue to estimate depth of myometrial invasion in endometrial adenocarcinoma is less reliable as the grade of the tumor increases. Alternative methods, such as frozen section, should be considered when evaluating depth of invasion, especially when this affects intraoperative decisions regarding lymph node sampling.

Adenocarcinoma↗

Gunshot wounds to the gravid uterus. A case report.

A pregnant woman sustained an abdominal gunshot wound during the second trimester; the bullet injured multiple loops of bowel and passed through the uterus, placenta and fetus. Although the stillborn fetus was delivered by cesarean section, a review of the literature indicated that operative delivery is not indicated when the fetus has died already. Labor and delivery are well tolerated, and an unnecessary hysterotomy is thus avoided. If labor does not ensue spontaneously, it can be induced. Approximately 40% of fetuses will survive the initial injury. In past reviews the risk of prematurity often outweighed the benefits of delivery of those infants. Advances in neonatology now make survival routine after 28 weeks' gestation, and viable fetuses should be delivered promptly by cesarean section to decrease the risk of delayed death from fetal or placental injury.

Adult↗

Recurrent ovarian granulosa cell tumor: role of combination chemotherapy with report of a long-term response to a cyclophosphamide, doxorubicin and cisplatin regimen.

We report a patient who, at age 43, underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for an unrupted 10 cm granulosa cell tumor. A recurrence was subtotally totally resected 2.5 years later, followed by six cycles of cyclophosphamide, doxorubicin, and cis-platin (CAP) chemotherapy. She had no evidence of disease at second-look laparotomy. Serum estradiol (E2) levels paralleled her clinical course, becoming elevated at the time of her recurrence, and returning to postmenopausal levels during her chemotherapy. Four years later, further elevation in E2 heralded a second recurrence of tumor. The patient underwent a cytoreductive procedure and has resumed chemotherapy. Reports of the few other patients treated with multiagent chemotherapy are reviewed. Several combinations appear active, with the CAP regimen having possibly less toxicity. Compared with radiotherapy, chemotherapy may yield longer survival in patients with recurrent granulosa cell tumor, but actual cure remains elusive.

Adult↗