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Unlabelled: Clinical usefulness of sentinel lymph node (SLN) biopsy has been demonstrated in the management of early vulvar cancer. However, what constitutes a negative SLN has not been well defined. Furthermore, to what extent the SLNs should be sectioned for the greatest likelihood of detection of micrometastases and whether multilevel sectioning will further increase this detection rate in this setting have not been well studied. We analyzed 280 groin lymph nodes (SLNs=45, non-sentinel [NSLNs]=235) in 14 patients with invasive squamous cell carcinoma (ISCC) of the vulva treated with vulvectomy and inguinal SLN and NSLN dissection at the H. Lee Moffitt Cancer Center (HLMCC) between 1996 and 2001. Each SNL was evaluated for micrometastases by H&E and pancytokeratin AE1/3 (CKAE1/3) immunohistochemical staining. All negative SNLs (N=40) were sectioned times 3 (x3) at 50-micron intervals and independently reviewed by two pathologists in order to assess the utility of this inexpensive and logical approach to identifying additional micrometastases. Also, the Wilcoxon Rank Sum Test was used to determine if there was an association between tumor size, depth of invasion and SNL status. The patient age ranged from 35 to 81 years (mean 59 yrs); size of invasive tumor from 1.0 to 7.0 cm (mean 3.4 cm); depth of invasion from 3 to 25 mm (mean 10.8 mm). Of 45 SLNs examined from 14 patients, 11% (5/45) SNLs were positive for micrometastases on initial H&E and/or CKAE1/3 stains. Eighty-nine per cent (40/45) SNLs were negative in the remaining 9 patients. None of the latter 40 SNLs showed micrometastases on additional multilevel sectioning. Instead 3 of 135 NSLNs examined in these 9 patients revealed micrometastases on H&E (skip-micrometastases). Mean tumor size (cm) and depth of invasion (cm) were 4.06 (s.d. 1.89) and 1.20 (s.d. 0.35) for SLN (+) and 3.02 (s.d. 2.12) and 1.01 (s.d. 0.86) for SLN (-) tumor subsets (p values 0.385 and 0.348, respectively)., Conclusion: Following routine H&E and CK AE1/3 stains, multilevel sectioning does not appear to detect additional micrometastases in sentinel lymph nodes in squamous cell carcinoma of the vulva. Even though mean tumor size and depth of invasion were greater in SNL (+) as compared to SLN (-) tumor subsets in our series, this difference did not reach statistical significance.

Objective: Cisplatin is a standard treatment in advanced, recurrent cervical cancer. Because topotecan is an established treatment in gynecologic malignancies such as ovarian cancer and exhibits nonoverlapping toxicity with cisplatin, a phase II trial was conducted to evaluate the tolerability and antitumor activity of a cisplatin/topotecan doublet in persistent or recurrent cervical cancer patients., Methods: Patients with bidimensionally measurable persistent or recurrent squamous cell and non squamous cell cervical cancer and adequate bone marrow were enrolled. Patients received 50 mg/m(2) of cisplatin intravenously over 1 h on Day 1 and 0.75 mg/m(2) of topotecan intravenously over 30 min on Days 1, 2, and 3 of 21-day cycles for six cycles or until disease progression. Tumor response and regimen toxicity were assessed using established Gynecologic Oncology Group criteria., Results: Thirty-two of 35 enrolled patients were evaluable for toxicity and tumor response. All but 2 evaluable patients had received previous radiotherapy. No patient received prior chemotherapy. The cisplatin/topotecan doublet was well tolerated, with 77 and 78% of courses given without interruption or delay and at full doses, respectively. As anticipated, the most common toxicity was hematologic, with grade 3/4 neutropenia and thrombocytopenia reported in 30 and 10% of cycles, respectively. The overall response rate was 28% (9/32), with 3 complete and 6 partial responses. The antitumor response in nonirradiated fields (30%) was similar to the response observed in previously irradiated fields (33%), suggesting good drug penetration. Median duration of response was 5 months (range, 2 to 15+ months). An additional 9 (28%) patients achieved stable disease. Median survival was 10 months, with 3 patients in lasting remission., Conclusions: These results demonstrate that the cisplatin/topotecan combination is safe, well tolerated, and active in persistent or recurrent cervical cancer patients. A phase III, multicenter trial is under way (cisplatin/topotecan versus cisplatin) based on these favorable results to confirm the safety and efficacy profile in this patient population.

Purpose: The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva., Materials and Methods: In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor., Results: From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3. 2 cm (0.5-7.0) and the mean depth of invasion was 9.1 mm (1.1-28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa., Conclusion: The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies., (Copyright 1999 Academic Press.)

Forty-five patients who underwent a modified radical vulvectomy for invasive squamous cell carcinoma of the vulva were compared with forty-five patients who underwent radical vulvectomy for similar lesions. Vulvar wound infection and breakdown were infrequent in both groups. Anal incontinence developed postoperatively in five of the modified radical vulvectomy patients and in none of the radical vulvectomy patients. Urinary incontinence developed postoperatively in two of the modified radical vulvectomy patients and in seven of the radical vulvectomy patients. Possible reasons for these differences are discussed. One invasive local recurrence (2.2%) developed in the modified radical vulvectomy group and two (4.4%) local recurrences developed in the radical vulvectomy group. A modified radical vulvectomy appears to be efficacious for the vulvar phase of treatment of localized invasive squamous cell carcinoma of the vulva.

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.

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 is an uncommon malignancy, accounting for 5% of gynecologic cancers. Patients who have locally advanced disease often cannot be managed locally by a radical vulvar resection. Current approaches to the treatment of locally advanced vulvar cancer include ultraradical surgery, radiotherapy, or a combination of treatment modalities. Ultraradical surgery has been used for patients with clinically resectable vulvar lesions and generally has consisted of a radical vulvar operation combined with a partial or total pelvic exenterative type procedure. The use of primary radiotherapy for carcinoma of the vulva remains controversial but may be the only option available when the patient has unresectable disease. Data have accumulated to confirm that megavoltage radiotherapy can cause marked regression of even locally advanced vulvar carcinoma to the point where a more limited resection can then be undertaken, often with an improved resection margin, with sparing of organ function, and improved quality of life. As with preoperative radiotherapy, combined chemoradiotherapy with or without resection has been used increasingly, with some promising results in several squamous cell carcinomas. There are few data on this type of treatment for carcinoma of the vulva.

Cisplatin, bleomycin, and mitomycin-C were used to treat 25 patients with recurrent squamous cell carcinoma of the cervix. Six patients had a partial response, yielding a total response rate of 27%. Nine patients had stable disease. The median survival for the whole group was 30 weeks. The median survival for responders was 32 weeks. The median progression free interval for the whole group was 12 weeks and the median progression-free free interval for responders was 14 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, bleomycin, and mitomycin-C has modest effectiveness in the treatment of recurrent squamous cell carcinoma of the cervix, but represents no improvement over single-agent chemotherapy.

Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population.

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.