Prognostic impact of lymphadenectomy in clinically early stage malignant germ cell tumour of the ovary.

BACKGROUND: The aim of this study was to determine the impact of lymphadenectomy and nodal metastasis on survival in clinical stage I malignant ovarian germ cell tumour (OGCT). METHODS: Data were obtained from the National Cancer Institute registry from 1988 to 2006. Analyses were performed using Student's t-test, Kaplan-Meier and Cox proportional hazard methods. RESULTS: In all, 1083 patients with OGCT who have undergone surgical treatment and deemed at time of the surgery to have disease clinically confined to the ovary were included 590 (54.48%) had no lymphadenectomy (LND-1) and 493 (45.52%) had lymphadenectomy. Of the 493 patients who had lymphadenectomy, 441 (89.5%) were FIGO surgical stage I (LND+1) and 52 (10.5%) were upstaged to FIGO stage IIIC due to nodal metastasis (LND+3C). The 5-year survival was 96.9% for LND-1, 97.7% for LND+1 and 93.4% for LND+3C (P=0.5). On multivariate analysis, lymphadenectomy was not an independent predictor of survival when controlling for age, histology and race (HR: 1.26, 95% CI: 0.62-2.58, P=0.5). Moreover, the presence of lymph node metastasis had no significant effect on survival (HR: 2.7, 95% CI: 0.67-10.96, P=0.16). CONCLUSION: Neither lymphadenectomy nor lymph node metastasis was an independent predictor of survival in patients with OGCT confined to the ovary. This probably reflects the highly chemosensitive nature of these tumours.

The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington between January 1990 and January 2000 were eligible; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). RESULTS: Age was < 45 years in 15% of patients, between 46 and 64 years in 47% of patients, and > 65 years in 38% of patients. Younger patients were statistically more obese than older patients (Body Mass Index of 40.3 kg/m2 vs. 35.3 kg/m2 vs. 31.0 kg/m2, P < 0.001). Intraoperatively, there were no differences between the three groups in the percentage of patients with lymph node sampling, operative time, blood loss, or complications. Postoperatively, older patients had more wound infections (P = 0.002), more cardiac events (P = 0.001), and more episodes of ileus (P = 0.025). Evaluation of pathology revealed that patients < 45 years old were statistically more likely to have endometrioid histology, grade I tumors, and stage IA disease. Women over age 65 were significantly more likely to have papillary serous histology, grade 3 tumors, and stage IC as compared to the younger patients. A subset analysis of patients > 75 years of age showed an increase in the percentage of patients with papillary serous histology (22% vs. 3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease (21% vs. 3%, P = 0.001) when compared to patients < 45 years old. Evaluation of endometrioid tumors only revealed a similar pattern of deeper myometrial invasion and higher tumor grade as age increased. CONCLUSIONS: Younger patients with endometrial cancer are generally more obese, with lower grade, lower stage disease, and with more favorable histologic cell types. Despite this, approximately a quarter have stage II-IV disease and 9% have positive lymph nodes. The older patients represent a dramatically different subset of patients. They are more likely to have aggressive papillary serous histology, higher grade tumors, and advanced stage disease. Age should be a consideration in appropriate referrals to gynecologic oncologists.

The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of body mass index (BMI) on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington, between 1 January 1990 and 1 January 2000 were eligible; 439 patients were identified and 43 were excluded due to incomplete medical records; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 27 months (range, 1 to 120 mo). RESULTS: Mean BMI was 34 (range, 15 to 69). BMI was <30 in 40.7% of patients, 30 to 40 in 32.3%, and >40 in 27.0%. Clinically, patients with a BMI of >40 were more likely to have hypertension, diabetes, and pulmonary disease. Those patients with a BMI of >40 had statistically longer operating times (209 vs. 159 min) and more blood loss (604 vs. 324 ml) than patients with a BMI of <30. However, there was no difference between the three groups in number of lymph nodes removed, units of blood transfused, length of hospital stay, number of intensive care unit (ICU) days, or intraoperative complications. Postoperatively, patients with a BMI of >40 were more likely to have a wound separation than thinner patients. Pathologically, patients with a BMI of >40 were more likely to have endometrioid histology, lower stage disease, and lower grade tumors than women with a BMI of <30. However, 11.3% of patients with lymph node sampling and a BMI of >40 had positive lymph nodes and 23% were stage II or higher. Forty-two patients (10.6%) recurred. There were no postoperative deaths, and there was no difference in survival between the three groups. CONCLUSIONS: Patients with a BMI of >40 frequently have favorable stage I endometrial cancers. However, approximately a quarter of these patients have evidence of cervical or extrauterine disease. This study confirms that surgical staging can be performed adequately and safely in morbidly obese patients with no difference in length of hospital stay, number of ICU days, intraoperative or postoperative complications.

Umbilical artery Doppler flow velocimetry in intrauterine growth restriction and its relation to perinatal outcome.

OBJECTIVE: The purpose of this retrospective analysis was to compare pregnancy outcomes in growth-restricted fetuses retaining normal umbilical artery Doppler flow and the outcomes of pregnancies with end-diastolic velocity either diminished or severely reduced/absent. METHODS: One hundred pregnant women with growth-restricted fetuses were followed with Doppler velocimetry of the umbilical artery between weeks 28 and 41 of pregnancy. Outcomes were compared for the normal Doppler group (16%), the less-severely abnormal group (77%), and the group with severely reduced or absent end-diastolic velocity waveforms (7%). RESULTS: The diagnosis-to-delivery interval was significantly shorter, and the average birth weight and gestational age at delivery were significantly lower, for fetuses with abnormal Doppler velocimetry (showing diminished or severely reduced/absent end-diastolic velocity) than for those in the normal Doppler group. Fetuses with abnormal Doppler velocimetry also had a significantly higher incidence of oligohydramnios, low-birth weight (<10th percentile), and admission to the Neonatal Intensive Care Unit. There were no perinatal deaths among the normal Doppler patients. CONCLUSIONS: Growth-restricted fetuses with normal umbilical artery velocimetry are at significantly lower risk than those with abnormal velocity waveforms, and immediate delivery of the fetus with diminished end-diastolic flow may be unnecessary. Knowing this relationship may be useful in the clinical management of such pregnancies. Doppler surveillance of growth-restricted fetuses supplemented with cardiotocography, preferably combined with biophysical profile testing, results in a prolonged gestational age and acceptable fetal outcome.

The use of angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction in community hospitals. Michigan State University Inter-Institutional Collaborative Heart (MICH) Study Group.

BACKGROUND: Previous studies documenting underutilization of angiotensin-converting enzyme inhibitors (ACEIs) in acute myocardial infarction (AMI) have been limited to Medicare populations. HYPOTHESIS: This study examines ACEI prescription rates and predictors in a community sample of hospitalized patients with AMI. METHODS: The charts of 1163 community patients with AMI, prospectively identified at admission between January 1, 1994, and April 30, 1995, were reviewed. RESULTS: Only 64 of 158 (40%) patients considered ideal candidates for ACEI prescription were discharged with a prescription for an ACEI. In a multivariate logistic regression model, prior ACEI utilization [adjusted odds ration (OR) = 3.26; 95% confidence interval (CI) = 2.05-5.20], presence of congestive heart failure (OR = 2.33; CI = 1.50-3.61) and black race (OR = 2.20; CI = 1.34-3.64) were identified as positive predictors of ACEI prescription. Conversely, lack of left ventricular ejection fraction (LVEF) measurement (OR = 0.46; CI = 0.28-0.75), LVEF > 40 ( OR = 0.27; CI = 0.18-0.40), and acute renal failure (OR = 0.08; CI = 0.01-0.44) were negative predictors. Women were also less likely to be discharged with an ACEI prescription (OR = 0.71; CI = 0.48-1.05). Furthermore, women were significantly less likely to have LVEF measured prior to discharge than were males (77 vs. 85%, p = 0.001). CONCLUSION: This study underscores the need for improvement in the utilization of ACEI in eligible patients with AMI. It also identifies opportunities for improvement in prescription rates, especially in women.

The prognostic significance of radiation dose and residual tumor in the treatment of barrel-shaped endophytic cervical carcinoma.

OBJECTIVE: The aim of this study was to evaluate the impact of total radiation dose on residual tumor and the prognostic significance of persistent disease in women with bulky, barrel-shaped cervical carcinoma who received definitive radiation followed by adjuvant hysterectomy. METHODS: The medical records of 57 patients with bulky endophytic cervical carcinoma treated at the University of Washington between 1976 and 1997 were reviewed. All patients received external beam pelvic radiotherapy supplemented by intracavitary brachytherapy, followed by extrafascial hysterectomy 6 to 8 weeks later. RESULTS: The mean pretreatment tumor diameter was 5.9 cm, with a range of 4-9 cm. Total radiation dose to point A ranged from 5040 to 9700 cGy, and the mean for the group was 7966 cGy. Residual disease was present in 35 (61%) of the hysterectomy specimens. The frequency of cervical tumor sterilization correlated significantly with the mean radiation dose to point A (P = 0.016). Patients without histologic residual disease had a significantly improved outcome, with 95% of patients remaining clinically free of disease at last follow-up, versus 31% of those with residual disease (P < 0.001). As expected, the pelvic control rate was excellent (100%) in patients with complete tumor eradication compared to the group with residual tumor (44%). Those with no residual disease enjoyed a significantly improved survival compared to those with residual tumor (P < 0.001). Furthermore, a statistically significant higher survival was realized in patients harboring only microscopic residual compared to those with either macroscopically evident tumor residuum and/or positive surgical margins (P = 0.036). CONCLUSIONS: Higher radiation doses are associated with an improved likelihood of tumor eradication in the treatment of bulky, endophytic cervical cancer and complete tumor sterilization at adjuvant hysterectomy is predictive of significantly enhanced survival and pelvic control. The high rate of histologic tumor persistence in our series emphasizes the need for more efficacious therapies in patients with bulky endophytic cervical cancer and argues for escalation of radiation dose even when adjuvant hysterectomy is planned.

Stillbirths in Qatar: a review of 83 cases.

To evaluate the aetiology, diagnostic procedures and current management of stillbirths in Qatar, 83 stillbirths with a birth weight of more than 500 g were studied. The validity of the cause of death was classified as certain, probable and unexplained. Frequency and descriptive statistics were used. The stillbirth rate was 8.15 per 1000. The cause of death was certain in 29%, probable in 62% and remained entirely unexplained in 9% of the cases. The major factors that might be the causes of fetal death were intrauterine growth retardation (23%), abruptio placentae (16.3%), congenital anomalies (13.3%), gestational diabetes (9.6%) and hydrops fetalis (7.2%). The cause of death was found unavoidable in 24 cases (29%). The autopsy rate was terribly low (1/80) and far away from the recommended rate of 75%. The introduction of a stillbirth programme, that includes post-mortem autopsy, in any maternity hospital, is considered crucial to reach a specific diagnosis for almost all stillbirths and to prevent fetal death in future pregnancies. However, if the patient or her family refused autopsy, a combination of patience and learned communication can pave the way to their understanding and acceptance of the procedure. Postmortem magnetic resonance imaging may be used as alternative to autopsy if it is refused.

Pretreatment scalene node biopsy in gynecologic malignancy: prudent or passé?

OBJECTIVES: Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. MATERIALS AND METHODS: We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. RESULTS: Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade >/=3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. CONCLUSIONS: Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Impact of surgical staging in women with locally advanced cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the impact of surgical staging in the treatment and outcome of women with locally advanced cervical cancer. METHODS: Ninety-eight women with locally advanced cervical cancer treated between 1993 and 1997 were retrospectively reviewed. Survival probabilities were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: Of the 98 women treated over the 5-year period, 86 were surgically staged: 61 by a retroperitoneal approach, 18 by laparoscopy, and 7 by laparotomy. Median blood loss was 120 cc and median length of hospitalization was 3 days. Preoperative CT scans (n = 55), when compared with surgical findings, missed macroscopic nodal disease in 20% and microscopic disease in 15% and overcalled disease in 10% of cases. Lymph node metastases were found in 45/86 patients (52%): 12 microscopic and 33 macroscopic. The highest level of nodes found to be involved was pelvic in 23, common iliac nodes in 3, para-aortic nodes in 14, and scalene nodes in 5 cases. Of the 86 patients, 49 received pelvic radiation, 27 received extended field radiation, and 10 were identified for palliative treatment only (5 scalene node metastasis, 5 extensive intraperitoneal disease). For node-negative patients, 5-year survival was 74%; for microscopic nodal involvement it was 58%; and for macroscopic involvement it was 39% (P = 0.007). Five-year survival for women with para-aortic node involvement was 52%. Number of nodes involved was a significant prognostic variable (P = 0.008). Patients who received chemotherapy had a 5-year survival of 68% compared to 35% for those who did not (P = 0.06). Factors which did not affect survival included age, histology, type of surgery, stage, and type of radiation (pelvic vs extended). CONCLUSION: Surgical staging of women with locally advanced cervical cancer can be performed with acceptable morbidity and it provided more accurate information than CT scans and resulted in a modification of the standard pelvic radiation field for 43% of our patients. The information obtained from surgical staging allows better individualization of therapy, which may improve overall clinical outcome.

Methotrexate compared with mercaptopurine for early induced abortion.

OBJECTIVE: To compare the antimetabolites methotrexate and 6-mercaptopurine as single-agent medical abortifacients using clinical and immunohistochemical analyses. METHODS: Twenty-seven women with gestations less than 7 weeks from the last menstrual period (LMP) were randomized to receive intramuscular methotrexate, 50 mg/m2, or oral 6-mercaptopurine, 200 mg. Forty-six additional women received methotrexate after randomization was discontinued. Women returned at 2-week intervals. Those without fetal cardiac activity were followed until complete abortion. Those with fetal cardiac activity were considered failures and underwent suction abortions. Tissue collected at the time of suction abortion was analyzed with the cell-proliferation immunohistochemical assay Ki-67. RESULTS: All 12 women in the 6-mercaptopurine group had fetal cardiac activity at follow-up and underwent suction abortion; therefore, this arm of the study was discontinued. Six of the 61 women who received methotrexate had fetal cardiac activity at follow-up and also underwent suction abortion. Fetal cardiac activity was present after methotrexate in three of 55 women at less than 6 weeks from the LMP and in three of six between 6 and 7 weeks from the LMP (P < .01). Women who aborted after methotrexate started bleeding on day 19 (standard deviation [SD] 7.8), bled for 9 days (SD 4.0), and used minimal pain medications. Tissues exposed to methotrexate showed decreased Ki-67 activity compared with tissues exposed to 6-mercaptopurine (P = .003). CONCLUSION: In oral doses of 200 mg, 6-mercaptopurine did not induce early abortion. A single intramuscular dose of methotrexate used without prostaglandins induced abortion in most women at gestational ages of less than 6 weeks. Ki-67 activity was lower in a small sample of fetal tissues exposed to methotrexate than in tissues exposed to 6-mercaptopurine.

A new technique for performing Syed template interstitial implants for anterior vaginal tumors using an open retropubic approach.

The Syed template (Alpha-Omega Services, Bellflower, CA) has been established as an advance in interstitial gynecologic brachytherapy. Unfortunately, enthusiasm for the technique is often tempered by certain tumor geometries which require blind insertion of the interstitial needles, potentially risking inaccurate placement of the radioactive sources and viscus perforation. These concerns arise particularly in the management of anterior vaginal tumors where difficulties in negotiating the pubic arch can prevent optimal needle placement. In answer to this problem, a technique utilizing an open retropubic approach for Syed template interstitial implants in anterior vaginal tumors under direct visualization is described. To date, six procedures have been performed. The disease entities include advanced cervical squamous cell carcinoma, clear cell carcinoma of the vagina, recurrent vaginal carcinoma, recurrent endometrial carcinoma, and urethral adenocarcinoma. Complete response was noted in five of six patients but persistent local control of disease was achieved in only one of five complete responses over a relatively short follow-up interval. Complications included paravaginal abscess (n = 1), postoperative deep venous thrombosis (n = 1), abdominal incision cellulitis (n = 1), and radiation enteritis (n = 1). An open retropubic approach allows direct visualization of the bladder and urethra during interstitial implantation of anterior vaginal malignancies and facilitates negotiation of the pubic arch. In our experience, this technique results in improved needle positioning and is thus intuitively likely to aid in avoiding injury to surrounding normal tissues. Additional accrual of a larger cohort will be necessary to arrive at any meaningful objective conclusions regarding the technique's benefit over current modalities.

Oncogene expression: long-term compared with short-term survival in patients with advanced epithelial ovarian cancer.

OBJECTIVE: To determine if oncogene overexpression in patients with advanced epithelial ovarian cancer correlates with survival. METHODS: Twenty-two women with stage III ovarian cancer, observed for a median of 66 (range 48-204) months were compared with 30 with a median survival of 18 (range 2-28) months. Using immunocytochemistry, tumors were immunostained for overexpression of p53, c-erb-B-2, and epidermal growth factor receptor and were evaluated quantitatively for expression of estrogen receptor, progesterone receptor, and Ki-67 antigen, a marker of cellular proliferation. RESULTS: The median age of long-term survivors was 52 (range 30-76) years compared with 55 (range 36-80) years for short-term survivors. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors compared with seven of the 30 short-term survivors, a significant difference (P=.05). The average level of Ki-67 expression was 43% in long-term survivors and 64% in short-term survivors (P=.007). Overexpression of p53 was seen in 54% of long-term survivors and 80% of short-term survivors (P=.05). A combination of Ki-67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term survivors compared with 68% of short-term survivors (P=.005). Epidermal growth factor receptor, c-erb-B-2, estrogen receptor, and progesterone receptor statuses did not differ significantly between the two groups. CONCLUSION: Markers that did not correlate with survival included the hormone receptors, estrogen receptor and progesterone receptor, and the oncogenes, c-erb-B-2 and epidermal growth factor receptor. Long-term survivors with advanced ovarian cancer were more likely to have had an optimal cytoreduction and lower levels of Ki-67 antigen expression and were less likely to overexpress p53 than were short-term survivors.

Adenocarcinoma of the uterine cervix metastatic to lymph nodes.

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined.

Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients.

OBJECTIVE: Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. METHODS: Patients with UPSC were identified from surgical pathology files and charts were retrospectively reviewed. Only patients who had undergone a TAH-BSO, lymph node dissection, and peritoneal cytology were included. RESULTS: The FIGO stages of the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5 IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

A retrospective review of paclitaxel-associated gastrointestinal necrosis in patients with epithelial ovarian cancer.

Seven patients with gastrointestinal necrosis following paclitaxel chemotherapy are reported. Four of seven patients had platinum refractory disease, while 3/7 patients received primary paclitaxel therapy. Complications occurred 5 to 16 days following paclitaxel therapy. The most common clinical presentation was fever (7/7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 patients). All seven patients developed gastrointestinal necrosis following the first cycle of paclitaxel chemotherapy. The exact mechanism by which this complication occurs is poorly understood. We postulate that gastrointestinal necrosis may be the result of a direct drug effect on the gastrointestinal epithelium and might involve a synergistic interaction between compromised bowel and paclitaxel-induced mitotic arrest. We observe that the incidence of gastrointestinal necrosis in patients with platinum refractory disease is 4 of 108 patients (3.7%). The incidence of this complication in patients receiving primary paclitaxel at our institution is 3 of approximately 128 patients (2.3%). Eighteen cases to date have been identified in the literature. A high index of suspicion of this complication should be considered for patients presenting with neutropenic fever and abdominal pain following paclitaxel chemotherapy.

Telomerase activation in cervical cancer.

It has been hypothesized that infection with high-risk human papillomaviruses (HPVs), in conjunction with other cellular events, plays a critical role in the development of cervical cancer. Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, has been associated with acquisition of the immortal phenotype in vitro and is commonly observed in human cancers. In this study, we have examined 10 high-grade cervical cancers for telomerase activity and for the presence of HPV. Telomerase activity was detected in all of the cancers but in none of the paired histopathologically normal uterine tissues or in normal cervical epithelium. Analysis of these same tissues for HPV nucleic acids by polymerase chain reaction (PCR) using primers from the HPV L1 and E6 open reading frames demonstrated that 7 of 10 cancers were positive for HPV, 3 for HPV type 16 (HPV-16), and 4 for HPV-18. In one case, HPV-16 was detected in histopathologically normal uterine tissue, the same type as that detected in the cancer from the same patient. HPV DNA was not detected in 3 of 10 cancers. These results indicate that telomerase activation is common in high-grade cervical cancers and suggests that telomerase activity may be a useful diagnostic marker for the disease.

Serum inhibin and disease status in women with ovarian granulosa cell tumors.

OBJECTIVE: To determine if immunoreactive inhibin assayed in serum from women with granulosa cell tumors correlated with tumor burden, reflected response to treatment, or predicted recurrent disease. STUDY DESIGN: Serum samples were collected following bilateral oophorectomy (BSO) with or without other indicated surgery in 15 patients with granulosa cell tumors. Inhibin radioimmunoassay (RIA-Inh) was performed on all samples and results were correlated with tumor burden, disease status, and treatment response. RESULTS: Fifteen patients had serum assayed for inhibin with levels ranging from 0 to 7470 U/liter. In 4 patients with measurable recurrent disease, inhibin levels correlated directly with tumor burden (r2 = 0.96). Four patients had serum drawn during clinical remission and in all 4 patients elevated inhibin levels predated recurrence by a median interval of 11.5 months (range 7-20). The remaining 7 were treated for primary disease and were in clinical remission with a median follow-up of 33 months (range 9-53). Four of these 7 patients were surgically staged: 2 were FIGO Stage I and inhibin levels fell to 0 U/liter; 2 patients had metastatic disease (Stage IIc and IIIa) and their inhibin levels were found to be elevated following complete resection. The remaining 3 were not surgically staged, and all had elevated inhibin levels while in clinical remission, suggesting occult disease. Of the 15 total patients, 1 who was treated with chemotherapy for recurrent disease was followed with serial inhibin levels. She showed a complete response to therapy with inhibin levels falling from 975 to 0 U/liter with 15 months follow-up. CONCLUSIONS: Serum inhibin levels reflect tumor burden and may be valuable in assessing response to chemotherapy or predicting recurrent disease in women with granulosa cell tumors who have had BSO. Serum inhibin level evaluation should be incorporated into large-group trials of therapy for granulosa cell tumors.

Phase II study of high-dose cisplatin, etoposide, and cyclophosphamide for refractory ovarian cancer.

OBJECTIVES: A phase II trial of high-dose cyclophosphamide, etoposide, and cisplatin was done. STUDY DESIGN: Forty-eight patients with progressive or persistent disease and previous cisplatin-based chemotherapy and no paclitaxel therapy were entered for treatment on the basis of two cycles of cyclophosphamide (4500 mg/m2), etoposide (750 mg/m2), and cisplatin (120 mg/m2). RESULT: Seventy-four cycles were delivered. Six patients died during treatment (12.5%). Of 28 with measurable disease, there was a 25% response rate and 32% had stable disease. Median time to recurrence and survival were significantly different for minimal versus bulky disease (p = 0.0089, p = 0.0008, log rank) and for platinum-sensitive versus platinum-resistant disease (p = 0.18, p = 0.0012, log-rank). The number of prior regimens was not correlated with time to progression or survival. CONCLUSION: This study shows little advantage for high-dose protocols except for patients with a response to platinating agents and minimal residual disease.

Clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy in stage III disease.

Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the surgical specimen compared with one (3%) in the papillary serous group (P = 0.002). Ten women (42%) with clear cell histology experienced a thromboembolic event during the course of treatment, compared to six (18%) in the papillary serous group (P = 0.05). In the group with clear cell histology, overall, 70% of women had progressive disease. Fifty-two percent experienced clinical progression while receiving platinum-based chemotherapy. In addition, four patients were found to have progressive disease at second-look laparotomy. Only two patients had a pathologic complete response. In the group with papillary serous histology, 29% overall had progressive disease while on chemotherapy (P = 0.005). The median survival for the women with clear cell histology was 12 months compared to 22 months for those with papillary serous (P = 0.02). For women with clear cell histology, univariate analysis was used to evaluate prognostic factors. Age less than 50 was a poor prognostic factor (P = 0.045). The presence of endometriosis, thromboembolic event, or optimal cytoreduction were not prognostic factors (P = 0.67, P = 0.34, P = 0.39). Patients with advanced clear cell ovarian cancer have a poor response to conventional platinum-based chemotherapy and overall prognosis is poor.