Ely Brand

Rhabdomyosarcoma of the uterine cervix. Sarcoma botryoides

Twenty‐one cases of sarcoma botryoides of the uterine cervix, including four previously unreported cases, are reviewed. The age of the patients ranged from 5 months to 48 years, with a peak incidence in the group aged 14 to 18 years. Eighty percent of the patients are alive, with a mean follow‐up period of 68 months. Seventy‐five percent of the patients had Group I disease, of whom 88% are alive. Eleven of 14 patients (79%) receiving vincristine and dactinomycin based chemotherapy are alive. There were five patients with recurrent disease (24%) of whom two (40%) are alive. The prognosis for cervical sarcoma botryoides is similar to that of other female genital tract embryonal rhabdomyosarcomas. Primary therapy should consist of vincristine and dactinomycin based chemotherapy. Surgery should be guided by the response to initial chemotherapy and should attempt to conserve the function of the bladder, rectum, vagina, and ovaries.

Vulvovaginal melanoma: report of seven cases and literature review.

Five cases of primary vaginal melanoma were treated at UCLA Medical Center between 1976 and 1986. Two additional cases of melanoma arising at the junction of the vulva and vagina are presented. One of seven (13%) patients is alive, with a median time to recurrence of 7 months, and median survival of 31 months. Four of five vaginal melanomas were located in the distal vagina, and all were advanced at diagnosis (greater than 3 mm depth). Mean size was 3 cm. Initial therapy was local excision in four patients and radical surgery in three. All patients had suboptimal surgical margins: two vaginal primaries had positive margins after local excision, both recurred vaginally within 5 months. Two patients had margins less than 1 mm, one died of distant metastases, the other is alive with disease 30 months after radical distal vaginectomy and hemivulvectomy with post-op pelvic radiotherapy. Three patients had melanoma in situ at the surgical margins, and each had pelvic recurrences between 6 and 26 months. Five of seven cases developed local recurrence as the initial site of treatment failure. All five vaginal cases ultimately developed distant disease, but only two patients had distant disease without local-regional recurrence. Chemotherapy and immunotherapy enabled disease stabilization in three patients. The vulvovaginal junction at the introitus is a high risk site for vaginal and vulvar melanoma. Intraoperative management requires assessment of lateral and deep spread of invasive and in situ melanoma.

In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines ☆ ☆☆ ★ ★★

OBJECTIVE Our goal was to determine whether toxicity of the diphtheria toxin A-chain gene regulated by the human chorionic gonadotropin promoter can be directed to malignant ovarian cell lines. STUDY DESIGN Plasmids containing diphtheria toxin A-chain gene linked to the regulatory elements of the metalloergothioneine and human chorionic gonadotropin promoters were transfected into the cell lines. Expression of diphtheria toxin A-chain gene was determined by the inhibition of a cotransfected luciferase reporter gene. RESULTS Cytotoxicity of the diphtheria toxin A-chain gene is shown in a dose-responsive manner. Transfection of a plasmid expressing the diphtheria toxin A-chain gene controlled by a constitutive promoter readily inhibits protein synthesis. Specific inhibition of luciferase protein synthesis occurs in ovarian cancer cells transfected with the diphtheria toxin A-chain gene under the control of the human chorionic gonadotropin promoters when compared with normal ovarian epithelial cells or fibroblasts. CONCLUSIONS These data demonstrate the preferential expression of the diphtheria toxin A-chain gene, regulated by the human chorionic gonadotropin promoter, to ovarian cancer cell lines. This provides an avenue for targeting such cells for suicide, toxin, or cytokine genes.

Photodynamic therapy of human choriocarcinoma transplanted to the hamster cheek pouch

Photodynamic therapy (PDT) uses light-activated compounds, such as hematoporphyrins, to produce cytotoxic effects after illumination. Human choriocarcinoma cells were transplanted into the hamster cheek pouch to study PDT. The transplanted choriocarcinoma secretes human chorionic gonadotropin (hCG) in proportion to tumor volume. Red light (630 nm) from an argon-pumped dye laser (100-200 J/cm2) was used to illuminate tumors sensitized with dihematoporphyrin ether (DHE). Previous work has demonstrated complete regression (CR) of 90% of tumors (18/20) after one or two PDT sessions, while contralateral cheek pouch tumors continued to grow despite intraperitoneal DHE. Neither DHE nor laser light alone resulted in significant CRs. In this study we evaluated intratumoral injection of DHE followed in 2 hr by laser treatment. In all tumors, localization of DHE was demonstrated by induced fluorescence with ultraviolet light or He:Cd laser. After a single treatment, 14 of 38 tumors (37%) completely regressed (hCG less than mIU/ml); 4 tumors regressed grossly with low-level hCG [partial regression (PR)]. After repeat treatment there were 10 additional CRs in 19 rapidly enlarging tumors. After a third treatment 3 CRs and 3 PRs were achieved in 6 tumors. Because of large volumes, 2 of 3 progressing tumors failed to fluoresce uniformly after intratumoral DHE and were treated after intraperitoneal DHE injection; both completely responded. Overall, 29 of 38 tumors (76%) completely responded to PDT, and 7 partially responded (18%) with no gross tumor remaining in 5 of the 7. Only 5% of tumors (2/38) were non-responders. Photodynamic therapy results in gross elimination of 90% of tumors (52/58) in this model after intraperitoneal or intratumoral DHE sensitization (P less than 0.0001). DHE in chorio-carcinomas is easily detected and may enable detection of occult foci of malignancy. Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy. Clinical trials of PDT in gynecologic cancers are warranted to confirm the high response rates observed in refractory nongynecologic cancers.

Rhabdomyosarcoma of the Uterine Cervix: Sarcoma Botryoides

Twenty-one cases of sarcoma botryoides of the uterine cervix, including four previously unreported cases, are reviewed. The age of the patients ranged from 5 months to 48 years, with a peak incidence in the group aged 14 to 18 years. Eighty percent of the patients are alive, with a mean follow-up period of 68 months. Seventy-five percent of the patients had Group I disease, of whom 88% are alive. Eleven of 14 patients (79%) receiving vincristine and dactinomycin based chemotherapy are alive. There were five patients with recurrent disease (24%) of whom two (40%) are alive. The prognosis for cervical sarcoma botryoides is similar to that of other female genital tract embryonal rhabdomyosarcomas. Primary therapy should consist of vincristine and dactinomycin based chemotherapy. Surgery should be guided by the response to initial chemotherapy and should attempt to conserve the function of the bladder, rectum, vagina, and ovaries.