James P. LaPolla

Invasive carcinoma of the vulva

Four hundred fifteen patients who had invasive carcinoma of the vulva were treated with primary surgery from July 1, 1955, through June 30, 1989. Three hundred seventy-six (90%) of the patients had squamous carcinoma. Two hundred fourteen patients (52%) had radical vulvectomy with inguinofemoral lymphadenectomy. Twenty-four patients (6%) underwent radical vulvectomy with pelvic exenteration for advanced disease, and 55 patients (13%) had nonradical operations. The remaining 122 patients (29%) underwent radical vulvectomy, inguinofemoral lymphadenectomy, and pelvic lymphadenectomy. The primary morbidity was associated with lymphedema (8.6%) and groin wound breakdown (54%). No intraoperative deaths occurred among the 415 patients treated surgically, but there were 17 deaths (4%) within 28 days of operation. The absolute 5-year survival rate was 85% in patients with negative inguinofemoral lymph nodes and 39% when these lymph nodes were positive for metastatic carcinoma. The overall absolute 5-year survival rate was 67%.

Ovarian management at the time of radical hysterectomy for cancer of the cervix

Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety-nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adenocarcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hysterectomy for early cervical cancer regardless of histologic type.

Concomitant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract

Twenty-three consecutive patients with advanced squamous carcinoma of the lower female genital tract were entered into a pilot study to determine the response rate and toxicity of a combination of intravenous cisplatin and 5-fluorouracil given concomitantly with radiation therapy. Twenty (87%) of the patients had a complete clinical response. Two patients (9%) had a partial response and one (4%) had stable disease. Nine (45%) of the complete responders have recurred with a median time to recurrence of 4 months. Seven (35%) had some component of local recurrence. The complete responders who have not recurred have been followed a median of 17 months. The acute toxicity was generally mild and there was no life-threatening acute complications. Three patients developed significant late complications. The response rate in this study was very high. The responses were usually prompt and dramatic, but often not sustained.

Interstitial radiotherapy for the treatment of advanced orrecurrent vulvar and distal vaginal malignancy

Summary From March 1, 1985 to April 30, 1988 10 patients with locally advanced primary orrecurrent vulvar or distal vaginal malignancy were managed with interstitial radiotherapy with or without teletherapy. One patient died of complications of a total pelvic exenteration for radionecrosis 8 months after completion of radiotherapy. The remaining nine patients were alive at a mean follow-up of 28 months (14 to 50 months). Recurrent disease developed within a bed of severe radionecrosis in two patients at 13 and 47 months after completion of radiotherapy. The remaining seven patients have remained without evidence of recurrent disease. Of the 10 total patients severe radionecrosis developed in six at a median of 8.5 months (6 to 26 months) after radiotherapy. We conclude from our data that the use of interstitial needles, mainly combined with external radiotherapy, for the treatment of locally advanced primary or recurrent vulvar and introital malignancy is highly effective but also highly morbid

Recent Modifications in the Treatment of lnvasive Squamous Cell Carcinoma of the Vulva

The curative potential of therapy should not be sacrificed. However, an effort must be made to determine methods that will reduce the morbidity while at least retaining the curative potential. Modifications which potentially may reduce the morbidity of regional nodal management include deletion of the inguinal lymphadenectomy or use of superficial inguinal lymphadenectomy in selected early lesions, the use of separate groin incisions, the selected use of unilateral inguinal lymphadenectomy, and the use of primary radiation therapy to the inguinal and/or pelvic nodal areas. Modifications which potentially may reduce the morbidity of the primary tumor management include wide local excision for superficial lesions, modified radical vulvectomy for regionalized lesions, the use of skin flaps in selected cases, the development of more sophisticated plastic surgical procedures for the management of posterior lesions, and the use of combined treatment modalities in the management of locally advanced disease.

Laser vaporization of grade 3 vaginal intraepithelial neoplasia

Between March 1, 1984, and May 23, 1990, 26 patients underwent laser vaporization for grade 3 vaginal intraepithelial neoplasia. Twenty of these patients had prior hysterectomy, 12 of them because of cervical neoplasia. Ten patients had undergone prior treatment for vaginal intraepithelial neoplasia. Eleven (42%) developed recurrence of vaginal neoplasia with a mean time to recurrence of 22 weeks. Three of the 11 patients had invasive cancer at the time of recurrence. One patient had invasive cancer on biopsy at the time of laser vaporization and subsequently underwent radiation therapy. The remaining 14 patients remain alive with no evidence of recurrent disease at a mean follow-up interval of 117 weeks. In our hands, laser vaporizaiton did not appear to be efficacious treatment for grade 3 vaginal intraepithelial neoplasia, especially when diagnosed in the region of a vaginal cuff scar.

Carcinoma of the vulva involving the perianal or anal skin

From January 1, 1985, to December 31, 1987, 58 patients underwent radical vulvar surgery for primary squamous cell carcinoma of the vulva. Twenty-four (41%) of the tumors involved the perianal or anal tissues. Nineteen patients had FIGO stage III disease and five patients had stage IV disease. Nineteen of the 24 patients underwent radical excision of their tumors, without colostomy. Two of the 19 excisions included resection of the majority of the anus, and both patients were subsequently left with severe fecal incontinence. In 8 patients the resection involved partial removal of the external and sphincter. Four of these patients developed persistent postoperative fecal incontinence. In the remaining 9 patients the resection involved partial removal of the anal skin, but with the external anal sphincter intact. One of these patients had postoperative fecal incontinence which was unchanged from her preoperative state. In conclusion, carcinoma of the vulva involving perianal tissue can be resected in most cases with adequate preservation of external anal sphincter function. If the sphincter is damaged during the operation, there is a significant risk for subsequent fecal incontinence.

A phase II trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy.

OBJECTIVES The efficacy and safety of bevacizumab and docetaxel were evaluated in women who developed recurrent epithelial ovarian, fallopian, or peritoneal cancer within 12 months of platinum-based therapy. METHODS Patients received docetaxel (40 mg/m(2)) on days 1 and 8 and bevacizumab (15 mg/kg) on day 1 of a 21-daycycle. Primary endpoint was 6-month progression-free survival (PFS). RESULTS Forty-one patients were evaluable for PFS and 38 for best response; 46% had platinum-free intervals (PFI) of <6 months and 54% between 6 and 12 months. The 6-month PFS was 43.9% (95% confidence interval (CI(95%))=28.6-58.2%). Median PFS (months) was 5.2 (CI(95%)=4.4-7.2) for all patients, 6.2 (CI(95%)=4.1-7.4) for patients with PFI <6 months, and 5.1 (CI(95%)=3.0-7.2) for those with PFI ≥ 6 months. Twenty-two patients showed overall response (CR+PR) (57.9%; CI(95%)=40.8-73.7%), and 32 showed clinical benefit (CR+PR+SD) (84.2%; CI(95%)=68.8-94.0%). For those with complete or partial responses, median duration of response was 4.8 months (0.7-14.5). Median overall survival was 12.4 months (CI(95%)=10.0-21.9). The most common grade 3/4 adverse events (AEs) were neutropenia (14.6% of patients), followed by leukopenia, fatigue, metabolic, and gastrointestinal, with 66% showing any grade 3/4 toxicity. Most common AEs of any grade were gastrointestinal (93%), fatigue (73%), and pain (73%). Four (10%) patients developed hypertension, 1 a gastrointestinal perforation, and another a colovesicular fistula. CONCLUSIONS Bevacizumab and docetaxel administered in patients with recurrent ovarian cancer is an active regimen without new unanticipated toxicities. This combination should be an option for further study or clinical use in recurrent ovarian cancer.

Management of radionecrosis of the vulva and distal vagina.

Twelve patients were seen between January 1983 and June 1989 with the clinical diagnosis of radionecrosis of the vulva or distal vagina. Seven patients received radiation for vulvar cancer, three for distal vaginal cancer, and two for recurrent endometrial cancer. No patient healed spontaneously and the mean delay in surgical therapy was 8.5 months. The radionecrotic site was treated with local therapy, radical local excision (with or without colostomy), or exenteration. The operative defect was closed primarily in three patients and covered with local flaps or myocutaneous flaps in seven patients. The two patients with local care still have radionecrotic ulcers. One of three patients who were closed primarily continues to have an ulcer. All other patients have healed satisfactorily except one who died after two attempts to correct the problem. Radionecrosis of the vulva and distal vagina should generally be treated surgically.

Experience with the EndoPap device for the cytologic detection of uterine cancer and its precursors: a comparison of the EndoPap with fractional curettage or hysterectomy.

Cytologic assessment of the endometrium with the EndoPap sampler was compared with curettage or hysterectomy in 249 women with symptoms. The sensitivities for the detection of primary corpus cancer and hyperplasia were 0.90 (59/66) and 0.58 (18/31), respectively. All six cases of atypical endometrial hyperplasia were detected by the EndoPap device. Malignant EndoPap cytologic findings were present in 4 of 10 patients with a primary adnexal malignancy and normal endometrial histologic findings. Ninety-two percent of primary uterine cervical cancers were detected by EndoPap cytologic sampling. The specificity for the cytologic diagnosis of benign conditions was 0.93. EndoPap cytologic sampling has a reasonably high sensitivity for the detection of uterine cancers and preinvasive endometrial lesions with a high risk of progression to carcinoma. Further evaluation as to its usefulness in a screening program for uterine and adnexal cancers in postmenopausal women should be considered.