Continuous intra-arterial cisplatin combined with radiotherapy in locally advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group pilot study.

The high local failure rate in patients with locally advanced carcinoma of the cervix treated with standard radiation has spurred interest in radiosensitization. Cisplatin is the most active single chemotherapeutic agent in squamous carcinoma of the cervix, and is considered to be a radiosensitizer. Based on a previous single-institution study looking at continuous low-dose intra-arterial cisplatin given throughout planned radiation therapy in patients with advanced carcinoma of the cervix, the Gynecologic Oncology Group initiated a limited access pilot study to assess the feasibility of this treatment method for a group-wide study. Patients with locally advanced squamous carcinoma of the cervix and surgically documented negative periaortic lymph nodes were eligible for the study. During surgical staging, the catheters of a totally implantable pump were placed in the internal iliac arteries. The pump was filled with cisplatin which was delivered at 4.5-6.5 mg day-1 continuously throughout both external radiation and brachytherapy. Drug distribution through the catheters was determined using radiolabelled macro-aggregated albumin particles. Three of nine evaluable patients were free of disease at follow-up. Drug distribution was less than optimal through 4.6% of the pump catheters. Five patients had premature discontinuation of the cisplatin for various reasons. These problems resulted in low accrual and subsequent closure of the study. This treatment method is not feasible for a phase III evaluation on a group-wide basis.

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.

Femoral vessel coverage with dura mater after inguinofemoral lymphadenectomy.

Twenty patients undergoing inguinofemoral lymphadenectomy for vulvar malignancy had the femoral vessels covered with freeze-dried human cadaver dura mater; 5 patients had a radical vulvectomy and 15 had a modified radical vulvectomy, and a total of 38 groins were explored. The dura mater was sutured to the inguinal ligament, sartorius muscle fascia, and adductor longus muscle fascia. Three of the thirty-eight wounds had wound breakdown uncovering the dura mater; each of the groins healed satisfactorily by secondary intention without exposing the femoral vessels. Three patients developed cellulitis without wound breakdown and three patients developed lymphocysts. All groin wounds have healed completely and there have been no delayed complications. The mean follow up was 12.5 months (range, 2-30 months). Coverage of the femoral vessels with dura mater after inguinofemoral lymphadenectomy appears to be a safe and effective alternative to the technically more difficult and more time-consuming sartorius muscle transplant.

Mass closure of the abdominal wound with delayed absorbable suture in surgery for gynecologic cancer.

There has been a resurgence of interest recently in the optimal method of closure of the midline abdominal wound. The focus has been on the high-risk patient in particular. The controversy centers on interrupted versus continuous fascial closure and the choice of suture material. For three years on a gynecologic cancer service, running mass closure with delayed absorbable suture (Polyglactin) was used. Two hundred fifty-six patients were evaluable for analysis. The minimum follow-up time was two years. There was no wound dehiscence. Fourteen patients (5.5%) developed incisional hernias. The mass closure technique using delayed absorbable suture was effective in very-high-risk patients.

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.

A phase II evaluation of cisplatin, bleomycin, and mitomycin-C in patients with recurrent squamous cell carcinoma of the cervix.

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.

Management of locally advanced squamous cell carcinoma of the vulva.

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.

Invasive carcinoma of the vulva. Changing trends in surgical management.

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%.

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.

Detection of endometrial carcinoma: clinical judgement versus histologic examination.

Dilatation and curettage (D&C) is routinely performed on patients with postmenopausal bleeding. The tendency is to rely on the results of the D&C rather than clinical judgment if the diagnosis is benign. In four of our patients treated with total abdominal hysterectomy, endometrial carcinoma was diagnosed even though earlier histologic examination with D&C had shown benign disease. All patients were 60 years of age or older. Three of the four patients had postmenopausal bleeding, and one patient had a Papanicolaou test that indicated an unexplained abnormality. All patients were obese (weighing more than 250 lb) and hypertensive. Other high-risk factors included diabetes mellitus in three and an elevated tumor marker antigen (CA125) in one. Frozen sections of tissue taken at D&C revealed no malignancy and failed to explain the postmenopausal bleeding. Rather than relying on these results, we assessed the high-risk factors and performed total abdominal hysterectomy immediately on all four patients. The results confirmed endometrial carcinoma. Immediate abdominal hysterectomy saved the patients additional anesthesia and delay in diagnosis.

Successful therapy of metastatic embryonal carcinoma coexisting with gonadoblastoma in a patient with 46,XY pure gonadal dysgenesis (Swyer's syndrome).

A case of gonadoblastoma associated with metastatic embryonal carcinoma occurring in a phenotypic female with 46,XY pure gonadal dysgenesis is presented. Two years after treatment with surgery and combination chemotherapy the patient is disease free. This is the third reported case and first reported cure in the English-language literature over the past 25 years. Current management is reviewed.

Interstitial radiotherapy for the treatment of advanced or recurrent vulvar and distal vaginal malignancy.

From March 1, 1985 to April 30, 1988 10 patients with locally advanced primary or recurrent 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.

Treatment of advanced gynecologic malignancies with intraarterial chemotherapy and accelerated fractionation radiation therapy: a preliminary report.

The results of a pilot study employing the administration of intraarterial chemotherapy and accelerated fractionation radiotherapy for advanced gynecologic malignancies are reported. The protocol consisted of three treatment sessions every 3 to 4 weeks. Each session consisted of bilateral or unilateral catheterization of the hypogastric artery with the infusion of cisplatin 100 mg/m2 on Day 1 and 2-deoxy-5-fluorouridine (FUDR) 300 mg/m2 on Day 2. An accelerated fractionation schedule of external-beam radiation was begun on Day 1 consisting of 200 rads twice daily for 4 days (1600 rads per session). Eight patients entered the protocol, and seven completed external-beam radiotherapy. Five completed three intraarterial sessions, and three, two sessions. Five of seven evaluable patients had a complete local response. Local control was sustained fom 6 to 24 months in four patients. Complications included three sensorimotor neuropathies, one clinically insignificant catheter-related thrombosis, and three clinically significant radiation injuries. This multimodality treatment for locally advanced gynecologic tumors appears feasible with modification, and continued work exploring this approach is encouraged.

Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy.

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.

Use of local flaps for primary anal reconstruction following perianal resection for neoplasia.

Perianal resection for neoplasia is associated with a significant risk for subsequent fecal incontinence. This report describes primary reconstruction of the anus using local skin flaps in nine patients who had undergone resection of perianal tissue for neoplasia. Seven patients had invasive cancer, and two patients had carcinoma in situ with a preoperative suspicion of invasive cancer. In all nine patients a portion of the external anal sphincter was excised during surgery. Bilateral rhomboid flaps were used in five patients, and four patients had advancement of local full-thickness skin flaps. All nine patients had a satisfactory anatomic result and were ultimately fecally continent.

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.

The management of diaphragmatic lesions in ovarian carcinoma.

Cytoreduction is currently an essential feature of the treatment of carcinoma of the ovary. Occasionally, optimal reduction is achieved except for localized diaphragmatic lesions. Two patients who were treated with primary cytoreduction for epithelial ovarian carcinoma had localized full-thickness diaphragmatic metastasis. Often resection is avoided because of concern about pneumothorax. A safe and easy method is described for removing peritoneal and diaphragmatic muscular metastasis without the need for a thoracostomy tube. These patients were cytoreduced without morbidity. The first patient is currently free of disease at 17 months after surgery. The second patient had a 13-month disease-free interval before her abdominal recurrence.

Use of Vicryl mesh in the reconstruction of the pelvic floor following exenteration.

Thirteen patients underwent reconstruction of the pelvic floor following pelvic exenteration using polyglactin 910 (Vicryl) mesh with omentum. One patient developed a conduit leak in the early postoperative period and one patient developed an enterocutaneous fistula at the time of recurrence. There were no other gastrointestinal or urinary tract complications. Six patients developed significant postoperative pelvic infections, four of which manifest as abscesses below the mesh. Vicryl mesh with omentum appears to be a reasonable method for reconstruction of the pelvic floor following exenteration. The postoperative infectious morbidity in this series is concerning, however.

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.

Whole-abdomen radiation as a second-line therapy for epithelial ovarian cancer.

Whole-abdomen irradiation was delivered to 11 patients with persistent epithelial ovarian cancer after chemotherapy. Ten of the eleven patients have recurred and subsequently died of disease. The median time to recurrence was 5.5 months. All 10 recurrences were within the irradiated field. All 6 patients with microscopic disease at second-look laparotomy recurred. Four of the five patients with minimal residual disease (less than or equal to 5 mm) at second-look laparotomy recurred. One patient is alive with no evidence of recurrence at 14 months. Four patients developed small bowel obstruction, three of which were associated with recurrence. During therapy, 4 patients developed significant enteritis and 5 patients developed significant bone marrow suppression. All 11 patients completed radiation therapy, although in 4 there were interruptions of 1 to 3 weeks. Whole-abdomen irradiation does not appear to be an effective second-line regimen for epithelial ovarian cancer, even in the presence of microscopic or minimal residual disease.