Jeffrey D. Bloss

Clinical and histologic features of vulvar carcinomas analyzed for human papillomavirus status: Evidence that squamous cell carcinoma of the vulva has more than one etiology

The association between the human papillomavirus (HPV) and malignant neoplasms of the uterine cervix is well established; however, its role in the pathogenesis of vulvar cancer has not been well defined. This study correlates the clinical and histopathologic features of 21 invasive carcinomas of the vulva with the presence of HPV DNA as detected by Southern blot and polymerase chain reaction (PCR) analysis. By one or both techniques, HPV DNA was detected in 10 of the 21 tumors analyzed; all HPVs containing tumors hybridized with HPV-16 probes, although PCR also detected HPV-6 in two of the HPV-16-containing tumors. No HPV-18 DNA was detected in any tumor by PCR or Southern blot hybridization. Both the invasive cancer and the surrounding intraepithelial disease tended to display histopathologic features that usually could distinguish HPV-associated cancers from those without HPV DNA. The intraepithelial lesions associated with HPV-containing tumors were of the bowenoid type with koilocytosis, while tumors lacking HPV generally demonstrated a simplex type of intraepithelial lesion. Invasive tumors with no viral DNA were more frequently keratinizing than the HPV-containing cancers. Race, parity, hormonal therapy, and alcohol use did not affect the HPV status; however, HPV DNA was more prevalent in the tumors of younger women and in those with a history of tobacco use. Human papillomavirus status had no impact on the stage of disease or its prognosis. These findings identify two subsets of vulvar carcinoma cases based on HPV hybridization data and the histopathologic characteristics of the tumor.

Randomized Trial of Cisplatin and Ifosfamide With or Without Bleomycin in Squamous Carcinoma of the Cervix: A Gynecologic Oncology Group Study

PURPOSE Phase II trial reports have suggested that the addition of bleomycin to the combination of cisplatin and ifosfamide may improve response rates and possible survival in squamous carcinoma of the cervix. This study prospectively evaluates the combination of bleomycin to this regimen in women with histologically proven advanced recurrent or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible women were randomized to receive either cisplatin (50 mg/m(2)), ifosfamide (5 g/m(2) over 24 hours), and mesna (6 g/m(2) during ifosfamide infusion and the following 12 hours) (CI) versus bleomycin 30 units over 24 hours on day 1 followed by cisplatin (50 mg/m(2)), ifosfamide (5 g/m(2) over 24 hours), and mesna (6 g/m(2) during ifosfamide infusion and the following 12 hours) (CIB). Three hundred three women were enrolled onto this trial, of which 287 were assessable. RESULTS There were no significant differences between CI and CIB with regard to response rates (32% v 31.2%, respectively), progression-free survival (PFS), or overall survival. PFS and survival were associated with initial performance status (PS). Patients with a PS of 0 experienced a lower rate of failure (P =.013) and a lower risk of death (P =.009) compared with patients with PS of 2. The most frequent grade 3/4 toxicities were leukopenia, neutropenia, anemia, thrombocytopenia, and nausea and vomiting. Neither regimen was associated with a significant increase in incidence of these toxicities. CONCLUSION The CI regimen was virtually identical to CIB with regard to response rate, PFS, survival, and toxicity profile. Thus, the addition of bleomycin in the dose-schedule employed to cisplatin and ifosfamide did not improve outcome in patients with advanced cervical cancer.

Use of vaginal hysterectomy for the management of stage I endometrial cancer in the medically compromised patient

Vaginal hysterectomy was performed on 31 patients with stage I endometrial cancer because of medical problems which placed them at high risk for morbidity and mortality from abdominal surgery. These risk factors included morbid obesity (87%), hypertension (58%), diabetes mellitus (35%), and cardiovascular diseases (26%). The perioperative morbidity was minimal, with only four patients (13%) experiencing complications requiring extended hospital stays and no deaths. Adjuvant radiotherapy was administered in 35% of patients with either deep myometrial invasion or unfavorable histology. The 3- and 5-year disease-free survival rates were 100 and 93%, respectively. The only cancer-related death occurred 4.5 years following surgery. Although the authors are not advocating vaginal hysterectomy as standard treatment of endometrial cancer, this approach provides an acceptable alternative to abdominal surgery in the medically compromised patient.

Vaginal hysterectomy as primary treatment of endometrial cancer in medically compromised women

Objective To study the survival, rates and patterns of recurrence, and perioperative morbidity in medically compromised women with endometrial cancer treated by primary vaginal hysterectomy. Methods Fifty-one patients with endometrial cancer treated initially by vaginal hysterectomy between 1977 and 1999 were identified at the University of California, Irvine Medical Center and affiliated hospitals. Data were retrieved from hospital and office records. Statistical analysis, including Kaplan-Meier methods, was performed and the disease-specific survival rates were estimated. This study has 80% power to demonstrate a greater than 20% improvement in 5-year survival over historical controls. Results Fifty-one women with uterine carcinoma clinically confined to the uterus underwent primary vaginal hysterectomy with (n = 26) or without (n = 25) salpingo-oophorectomy. Eighty-four percent were obese with a body mass index greater than 27. Additional risk factors for surgical complications included hypertension (57%), diabetes mellitus (27%), and cardiovascular disease (18%). One-third of patients had three or more risk factors. Surgical morbidity included one episode of acute hemorrhage necessitating transfusion and abdominal exploration. Blood transfusions were given to four additional patients. There were no perioperative deaths. Five women recurred and expired at a median of 13 months (range 3–53 months) after surgery. The 3- and 5-year disease-specific survival rates were 91.4% and 88.0%, respectively. Conclusion Vaginal hysterectomy for the initial treatment of early-stage endometrial cancer is associated with a high rate of cure and minimal morbidity. Thus, it may be considered a reasonable alternative to the abdominal approach in medically compromised women.

Comparison of adenocarcinoma and squamous cell carcinoma of the uterine cervix: A population-based epidemiologic study

OBJECTIVE Our objective was to compare epidemiologic and clinical characteristics of adenocarcinoma with those of squamous cell carcinoma of the cervix, with respect to risk by ethnic group, age at diagnosis, stage of disease at diagnosis, and survival. STUDY DESIGN All data were obtained from the Cancer Surveillance Program of Orange County, California, from 1984 through 1989. A total of 152 cases of adenocarcinoma and 457 of squamous cell carcinoma of the uterine cervix were included. RESULTS Adenocarcinoma of the cervix was diagnosed at a younger age and an earlier stage than squamous cell carcinoma. Hispanics have the highest risk for squamous cell carcinoma, whereas Asians have the highest risk for adenocarcinoma compared with whites. No differences were observed between the two histologic types in prognosis and survival. CONCLUSION Differences between the two histologic types of cervix cancer were found in the age at diagnosis, the extent of disease, and the ethnic distribution. In spite of these differences, prognosis and survival were not affected by histologic type.

Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy

The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulae and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high-risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity.

CA 125 regression: a model for epithelial ovarian cancer response.

The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method.

Radiation myelitis: A complication of concurrent cisplatin and 5-fluorouracil chemotherapy with extended field radiotherapy for carcinoma of the uterine cervix

Radiation myelitis is a rare but serious complication of radiation therapy. The total dose of radiation to the spinal cord required to cause myelopathy is greater than 50 Gy when the treatment is administered in 25 or more fractions; however, recent evidence has suggested that the concurrent use of chemotherapy may decrease the tolerance of the spinal cord to radiation. This report describes a case of radiation myelitis in a patient after concomitant fluorouracil/cisplatin chemotherapy and extended field radiotherapy for stage IIA adenosquamous cell carcinoma of the uterine cervix metastatic to the para-aortic lymph nodes.

Does intraperitoneal CA-125 reflect disease status?

The relationship of serum CA-125 to intraperitoneal (IP) CA-125 was studied in 45 patients with a variety of gynecologic diseases including ovarian carcinoma. In 43 of 45 patients the IP level exceeded the serum level of CA-125. Paracentesis may dramatically alter both levels, thus mimicking surgical debulking. All IP levels of CA-125 measured at second-look coeliotomy for the ovarian cancer patients were within the normal range of IP CA-125 measured at surgery for benign disease. Therefore, intraperitoneal CA-125 is less sensitive than serum CA-125 in predicting intraperitoneal disease status. Likewise it cannot be used to predict the subgroup of ovarian cancer patients with negative second-look coeliotomy who are destined to develop a recurrence of disease.

HEMOLYTIC-UREMIC SYNDROME ASSOCIATED WITH NEOADJUVANT CHEMOTHERAPY IN THE TREATMENT OF ADVANCED CERVICAL CANCER

Hemolytic-uremic syndrome (HUS) is a rare but severe complication of neoplastic disease as well as some of its treatments. The pathophysiology of HUS is poorly understood, but it affects multiple organ systems and carries a high mortality rate. The diagnosis of HUS is based on a clinical triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure, for which no proven therapies exist. This report describes a case of HUS developing in a patient with stage IVA squamous cell carcinoma of the uterine cervix following treatment with cisplatin/bleomycin/vincristine neoadjuvant chemotherapy prior to radiation therapy.