Ototoxicity after intraperitoneal chemotherapy: a case report.

Recently, the National Cancer Institute endorsed intraperitoneal (IP) therapy as the treatment of choice for optimally debulked epithelial ovarian cancer. However, there are no drug regimens that are clearly indicated, and the exact method of administration has not been established. Furthermore and most importantly, physicians are unaware of what toxicities should be expected with their use of IP therapy. We report a recent unanticipated toxicity from IP cisplatin therapy and review the literature. A 63-year-old female with optimally debulked stage IIIC papillary serous carcinoma of ovary was admitted on postoperative day 14 for her first cycle of IP cisplatin. She received a cisplatin infusion of 100 mg/m(2). Four days after the cycle, she suffered acute onset of bilateral tinnitus and hearing loss (ototoxicity grade 3). Thus, we conclude that high-frequency hearing loss remains a potentially serious and permanent adverse effect of cisplatin.

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Paclitaxel and platinum chemotherapy for ovarian carcinoma during pregnancy.

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Paclitaxel-based chemotherapy during pregnancy has not been reported previously. CASE: A woman with ascites and an adnexal mass diagnosed during pregnancy at 27 weeks gestational age underwent a laparotomy with cytoreductive surgery and was diagnosed with stage IIIC papillary serous ovarian adenocarcinoma. She was treated with three cycles of paclitaxel and cisplatin during pregnancy. At 37 weeks, she underwent a cesarean section, abdominal hysterectomy, and cytoreduction. Three additional cycles of chemotherapy were given. She developed a recurrence within 6 weeks of completing chemotherapy. She received several cycles of chemotherapy, but died of recurrent cancer 29 months after diagnosis. The infant has normal growth and development at 30 months of age. CONCLUSION: This is the first reported case of paclitaxel use during pregnancy.

The p53 mutational spectrum associated with BRCA1 mutant ovarian cancer.

PURPOSE: Cancer-specific p53 mutational spectra have been identified. Data from murine models and human BRCA1-related hereditary breast cancers suggest that both unique and specific BRCA1-associated p53 mutations may be found in BRCA1-related ovarian cancers. EXPERIMENTAL DESIGN: The p53 mutational spectrum from ovarian cancers containing either somatic or germ-line BRCA1 mutations was compared with that of sporadic ovarian cancers defined as those diagnosed with a negative family history for breast/ovarian cancer in a three-generation pedigree. Tumor DNA was screened over exons 2-11 of the p53 gene by the PCR and single-strand confirmation polymorphism analysis of the amplimers. Cycle-based DNA sequencing from separate reactions was used to confirm p53 mutations. RESULTS: p53 gene mutations were detected in 42 of 86 sporadic ovarian cancers, compared with 13 of 15 cancers with somatic BRCA1 mutations (P = 0.007) and 16 of 20 cancers with germ-line BRCA1 mutations (P = 0.01). p53 null mutations were found in 31.4% of BRCA1 mutant cancers, compared with only 9.3% of the sporadic cancers (P = 0.002). The p53 mutational spectrum of germ-line BRCA1-related cancers was shifted toward transversions, frameshifts, and non-CpG transitions relative to the spectrum of sporadic ovarian cancers. Thirty-three unique ovarian cancer p53 mutations were sequenced. However, the specific p53 mutations in the BRCA1 mutant cancers were no more unique to this cohort than the p53 mutations of the sporadic cancers. CONCLUSIONS: Ovarian cancers containing somatic or germ-line BRCA1 mutations are uniformly accompanied by p53 dysfunction. This finding offers additional support to observations regarding the importance of p53/BRCA1 interactions in ovarian carcinogenesis.

Ovarian function after surgical treatment for cervical cancer.

OBJECTIVE: Our previous analysis found a high rate of early menopause in cervical cancer patients with ovarian transposition (OT) compared to a group that underwent radical hysterectomy (RH) alone. The current study evaluates ovarian function in the same group for a prolonged follow-up period and analyzes predictive factors for early menopause. METHODS: One hundred two cervical cancer patients were treated with RH and/or lymphadenectomy and ovarian preservation from 1982 to 1989. A retrospective chart review was conducted, followed by a survey to determine the time of menopause. RESULTS: Eighty-three patients underwent RH and 19 patients underwent a staging laparotomy. Eighty procedures included OT. Twenty-six patients received postoperative radiation therapy. The mean follow-up for premenopausal patients was 87.0 months. The average age of menopause for the 13 nonradiated patients without unilateral oophorectomy (UO) or OT was 50.6 years. After OT without radiation therapy, 98.0% of patients retained ovarian function for a mean of 126 months with menopause at a mean of 45.8 years. When OT and radiation therapy were added, 41% retained ovarian function for a mean of 43 months and a mean age at menopause of 36.6 years. A multivariate analysis of nonradiated patients correlated age at diagnosis and a combination of OT procedure and UO with earlier ovarian failure. CONCLUSIONS: RH with bilateral ovarian preservation and without OT does not significantly reduce the age of menopause. The addition of UO or OT to this treatment reduces ovarian function appreciably. The addition of radiation therapy after OT dramatically shortens ovarian function.

Asymptomatic lung carcinoma presenting with a large vulvar lesion.

OBJECTIVE: Metastases to the vulva are infrequent, accounting for less than 10% of vulvar tumors. Vulvar metastases from lung carcinoma have been reported in two other cases. METHODS: A case of lung carcinoma metastatic to the vulva is reported. RESULTS: A 71-year-old woman was referred to The University of Iowa Hospitals and Clinics with a lung nodule on chest x-ray and a 12-cm, necrotic, left vulvar mass. A lung biopsy showed poorly differentiated carcinoma, and a palliative resection of the vulvar mass showed metastatic lung carcinoma. The patient died from sepsis on postoperative day 10. CONCLUSIONS: Lung carcinoma metastatic to the vulva is rare and portends a poor prognosis.

Pixel analysis of MR perfusion imaging in predicting radiation therapy outcome in cervical cancer.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast-enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long-term tumor control using pixel-by-pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast-enhanced MR imaging at the time of radiation therapy. Pixel-by-pixel statistical analysis of the ratio of post- to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long-term cancer follow-up (median follow-up 4.6 years; range 3.8-5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low-enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P = 0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long-term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027-1033.

Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva.

BACKGROUND: Traditional inguinal lymphadenectomy includes the removal of a portion of the saphenous vein. The authors hypothesized that preserving the saphenous vein would decrease morbidity without affecting treatment outcome. METHODS: A retrospective review of 83 patients with carcinoma of the vulva who underwent inguinal lymphadenectomy between 1990-1998 was performed. Postoperative short term and long term complications were evaluated. RESULTS: A total of 139 inguinal dissections were performed in 83 patients. The saphenous vein was preserved in 62 patients and ligated in 77 patients. The clinical characteristics of the patients, the operating time, and the estimated blood loss were not significantly different between the two groups. The incidence rate of short term complications including fever, seroma, phlebitis, lymphocyst, and deep venous thrombosis also was similar. Cellulitis occurred in 39% of the patients who underwent vein ligation compared with 18% of the patients who underwent a vein-sparing procedure (P = 0.006). Short term (< 6 months) lower extremity lymphedema occurred in 70% of the vein-ligated group compared with 32% of the vein-spared group (P < 0. 001). Chronic edema (>/= 2 years) was present in only 3% of the patients who underwent saphenous vein preservation compared with 32% of those who underwent vein ligation (P = 0.003). Chronic lymphedema in the vein-spared group was observed in only one patient who received postoperative radiation. Overall, individuals with preservation of the saphenous vein were less likely to develop complications (56% vs. 23%; P < 0.001). There was no difference in the rate of incidence of recurrent disease between the two groups. CONCLUSIONS: Preservation of the saphenous vein during inguinal lymphadenectomy reduces both the short term and long term postoperative complications without affecting treatment outcome. The saphenous vein should be preserved routinely in patients undergoing inguinal lymphadenectomy.

Longterm central venous access in gynecologic cancer patients.

BACKGROUND: To assess the utility and safety of three different longterm indwelling intravenous catheters in patients with gynecologic malignancies. STUDY DESIGN: A retrospective review was performed of the records of all women with gynecologic malignancies who required longterm venous access catheters and ports between 1990 and 1997. RESULTS: Two hundred sixty-eight women underwent placement of 308 indwelling catheters, of which 305 were available for analysis. Of those, 68 (22%) were Hickman catheters, 162 (53%) were infusaports, and 75 (25%) were Peripheral Access System (PAS) ports. Venous access was obtained percutaneously in 152 (50%) patients and by cutdown in 153 (50%). Prophylactic anticoagulation was used with 96 catheters (31%). Catheter placement was associated with 12 (4%) immediate complications and 87 (29%) delayed complications. The average duration of a catheter in place was 5.6 months for the Hickman, 12.5 months for the infusaport, and 16.0 months for the PAS port (p < 0.001). Bacteremia was more likely to develop in patients with Hickman catheters when compared with those with infusaports and PAS ports (19% versus 6% and 5%, respectively, p = 0.002). Thrombosis was significantly less likely to develop in patients receiving prophylactic anticoagulation (11% versus 4%, p = 0.004). Overall, the complication rate was lower with cutdown versus percutaneous access (p = 0.004). There was no statistically significant difference between the frequency of complications when correlated with the stage of disease, patient age, body mass index, or type of malignancy. CONCLUSIONS: Infusaports and PAS ports were associated with a lower risk of infection and have a longer life than Hickman catheters. The cutdown approach was associated with a lower complication rate. Low-dose prophylactic anticoagulation should be given to all patients with longterm central venous catheters.

Quality of life and mood in women receiving extensive chemotherapy for gynecologic cancer.

BACKGROUND: Quality of life (QOL) and mood were investigated among women who had received intensive chemotherapy for at least 1 year for advanced gynecologic cancers. Relationships of coping styles to QOL and mood in these patients also were examined. METHODS: Twenty-four patients who had been receiving chemotherapy continuously or intermittently for at least 1 year were recruited into the study. To control for the diagnosis of cancer and for prior hysterectomy, 24 age-matched early stage gynecologic cancer patients not receiving chemotherapy and assessed 1 year following diagnosis were examined as a comparison group. All subjects completed psychosocial assessments at a clinic visit. Medical information was retrospectively abstracted from patient charts. RESULTS: Decrements in physical, emotional, and functional well-being were reported by extensively treated patients, whereas social well-being and satisfaction with the relationship between doctor and patient were close to the norms of the comparison group. Extensively treated patients reported more fatigue and less vigor, but their depression and anxiety did not differ from early stage patients. Almost all extensively treated patients reported that their treatment had been worthwhile. Patients using avoidant coping reported poorer physical and emotional well-being, along with greater anxiety, depression, fatigue, and total mood disturbance. Those using active coping reported better social well-being, better relationships with their doctors, and less overall distress. CONCLUSIONS: This study indicates that gynecologic oncology patients extensively treated with chemotherapy experienced substantial decrements to quality of life, and yet treatment still was considered worthwhile by a majority of patients. Avoidant coping may be a particular risk factor for poor QOL and greater distress.

Docetaxel extravasation causing significant delayed tissue injury.

PURPOSE: Docetaxel is a relatively new taxane that has not been associated with significant tissue injury after extravasation. We present a case of a patient who had grade 4 tissue toxicity after extravasation of docetaxel infused through a peripheral intravenous site. CASE REPORT: A 71-year-old female was being treated for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the docetaxel infusion began, she experienced docetaxel extravasation into the dorsum of her left hand. The infusion was halted, and then the administration was continued in a peripheral intravenous site in the other upper extremity. Erythema was noted by the patient on the dorsum of her left hand 6 days after infiltration. The following day, the patient noted severe pain, decreased function, and blistering along with increased erythema. The patient presented to the gynecology oncology clinic 11 days after the extravasation injury occurred. Conservative management was undertaken, and over the next 4 weeks the patient had resolution of the skin changes and full return of function. CONCLUSION: Docetaxel can cause significant delayed tissue injury if extravasation occurs.

Cervical cancer diagnosed shortly after pregnancy: prognostic variables and delivery routes.

OBJECTIVE: To compare the prognoses of women diagnosed with cervical cancer during pregnancy with the prognoses of those diagnosed within 6 months after delivery and to assess the effect of vaginal delivery on recurrence risk and prognosis. METHODS: A matched case-control study of women with cervical cancer diagnosed during pregnancy or within 6 months of delivery was performed. Fifty-six women had cervical cancer diagnosed during pregnancy and 27 within 6 months after delivery. Controls (cervical cancer diagnosed at least 5 years since last delivery) were matched one-to-one with cases based on age, histology, stage, treatment, and time of treatment. RESULTS: Among postpartum women, four had stage IA disease, 15 had stage IB1 or IB2, and eight had stage IIA or higher disease. Eleven had radical hysterectomies and 14 had radiation therapy. Two with stage IA1 disease were treated with vaginal hysterectomies. One of seven patients who had cesareans developed a local and distant recurrence. In contrast, ten of 17 (59%) who delivered vaginally developed recurrences (P =.04). In multivariate analysis, vaginal delivery was the most significant predictor of recurrence (odds ratio [OR] 6.91; 95% confidence interval [CI] 1.45, 32.8), followed by high stage (OR 4.66; 95% CI 1.05, 20.8). The survival for patients diagnosed in the postpartum period was significantly worse than for controls. CONCLUSION: Women diagnosed postpartum had worse survival than those diagnosed during pregnancy and were at significant risk of recurrent disease, particularly if they delivered vaginally. Therefore, pregnant women with cervical cancer should be delivered by cesarean.

Surgical experiences and training of residents: perspective of experienced gynecologic oncologists.

OBJECTIVE: The aim of this study was to report the opinions of experienced gynecologic oncologists concerning the surgical education and experiences of residents. METHODS: The 1997 membership directory of the Society of Gynecologic Oncologists was used to identify individuals who were members for at least 5 years and on the faculty of residency training programs. One hundred seventy members were identified and a nine-question survey was mailed to them. RESULTS: One hundred nineteen (70%) surveys were returned. One hundred seventeen individuals were on the faculty of residency training programs and involved in the surgical training of residents. Ninety-six percent reported that gynecologic oncologists were a major resource for surgical education at their institution. Eight-nine (76%) reported a change in the volume of major abdominal and vaginal surgical procedures performed for noninvasive disease over the past 5 years. Of these 89, 16 (18%) reported that surgical volume at their institution decreased by 10%, 38 (43%) reported that surgical volume decreased by 10-25%, and 17 (19%) reported that surgical volume decreased by more than 25%. Sixty-three percent of all respondents reported that residents were not as well versed in pre- and postoperative care when compared to those of 5 years ago. Sixty-five percent of all respondents reported that graduating residents were less prepared in surgical techniques when compared to those of 5 years ago. Seventy-five percent of respondents reported that the primary care requirements of the RRC have decreased the amount of surgical experience, ICU rotations, and anesthesia rotations. Sixty percent of all respondents operated with other attending surgeons on more difficult cases, and 29% had changed to this practice within the past 5 years. Eighty-two percent believed that more time during residency training needs to be devoted gynecologic surgical experience. CONCLUSIONS: Experienced gynecologic oncologists on the faculty of residency training programs report a decrease in surgical skills and surgical experiences when compared to residents trained 5 years ago.

Distant metastases in ovarian cancer: association with p53 mutations.

Distant metastases are unusual occurrences at presentation and during the progression of epithelial ovarian cancer. There are no good clinical predictors of this phenomenon. Because p53 dysfunction is common in ovarian cancer, we chose to investigate whether specific types of mutations predicted a predisposition to distant metastasis. We hypothesized that the complete absence of intact p53 protein as seen with p53 null mutations may be associated with an enhanced tendency to develop distant metastatic disease. The complete coding sequence of 130 tumor DNA samples was screened for p53 mutations by single-strand conformational polymorphism analysis. Abnormal single-strand conformational polymorphism findings were correlated with the specific DNA sequence abnormalities and outcome. Ninety-four (72%) tumors carried p53 mutations. Sixty-two were missense mutations, and 32 were null mutations (6 nonsense mutations, 23 frameshift mutations, and 3 splice-site mutations). Twenty-eight patients were found to have distant metastases (pericardium, brain, parenchymal liver, spleen, or lung) either at presentation or during the course of their treatment. Distant metastases were nearly 8-fold more common in patients whose tumors carried a null mutation (66%) than in those with either missense mutations (8%) or wild-type p53 (8%; P<0.001). When a null mutation was present, 25% of the tumors were associated with distant metastases at initial diagnosis. No individual with wild-type p53 or a missense mutation in the tumor presented with distant metastasis. Tumors with null mutations were more likely to be associated with lymph node metastasis (P = 0.003), advanced stage (stage III/IV; P<0.001) and high grade (grade II/III; P<0.001), at presentation. These tumors progressed with distant metastases more swiftly than did tumors with either missense mutations (mean, 1.18 versus 2.71 years; P = 0.04) or wild-type p53 (3.57 years; P = 0.015). In contrast to the popular dogma, distant metastases in ovarian cancer do not necessarily result from prolonged treatment of disease. They may be predicted to occur early in the disease course due to a specific molecular genetic abnormality: null mutation of the p53 tumor suppressor gene. These findings need to be carefully considered when choosing between regional versus systemic treatment modalities.

Malignant cervical schwannoma: An unusual pelvic tumor.

BACKGROUND: Primary malignant cervical schwannomas (malignant peripheral nerve sheath tumors) are extremely rare tumors that grossly may resemble many other more common lesions. The diagnosis, management, and follow-up of a malignant cervical schwannoma are presented with a review of the literature. CASE: A 51-year-old female presented with a 3-year history of perimenopausal vaginal bleeding. A 3 x 3 cm friable, spongy lesion was noted on the posterior aspect of the cervix. Frozen-section analysis could not rule out a malignant smooth muscle tumor. The patient underwent an exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Immunohistochemistry and electron microscopy aided in the final diagnosis of a malignant cervical schwannoma. The patient is alive and well 1 year from her definitive surgery. Another patient with the same tumor received the same surgical management. This patient is now 10 years from her surgery and is alive with no evidence of disease. CONCLUSION: Immunohistochemistry and electron microscopy are useful in the diagnosis of a malignant cervical schwannoma. This case and long-term follow-up from another case provide evidence that simple hysterectomy may be sufficient therapy for this uncommon lesion.

Cyclosporin A reverses chemoresistance in patients with gynecologic malignancies.

Multidrug resistance is a major obstacle in successful systemic therapy of gynecologic malignancies. The objectives of this study are to evaluate the activity of cyclosporin A used to overcome drug resistance in a variety of gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the specific chemotherapeutic agent, to which the tumor had developed drug resistance. All patients had shown resistance to the chemotherapy agent used in combination with cyclosporin A. All patients had been heavily pretreated (mean, 2.8 previous chemotherapy regimens). Overall, among 38 available patients with gynecologic malignancies, a 29% objective response rate was observed. Twenty-six (65%) of all patients received three or more cycles of cyclosporin A. There was a 25% response rate for patients with ovarian cancer patients and 50% for those with uterine cancer. There were no responses among the three patients with cervical cancer, and the patient with choriocarcinoma had a complete response. All patients were evaluable for toxicity. Leukopenia and nausea were the most common toxic reactions, but in most cases they were transient, and only three patients required a treatment delay. The most common grade 3 or 4 toxicity was thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is well tolerated and has significant potential for reversal of chemoresistance in heavily pretreated patients with ovarian and uterine malignancies.

A case of severe hidradenitis suppurativa contributing to a death and a review of the literature.

OBJECTIVE: Our aim was to report a fatal complication of hidradenitis suppurativa and a review of the literature. MATERIALS AND METHODS: A case of severe hidradenitis suppurativa obscuring the diagnosis and precluding the treatment of a ruptured sigmoid diverticulum is presented. RESULTS: We describe a 48-year-old woman who had a long history of untreated hidradenitis suppurativa with extensive vulvar involvement and poor nutritional status. The advanced state of her disease on initial presentation led directly to her death. CONCLUSION: Although it is a treatable disease, hidradenitis suppurativa can lead to systemic sequelae severe enough to contribute directly to death.