Managing pain and psychological issues in palliative care.

The management of psychological issues and pain in dying patients have steadily improved. With currently available drugs and techniques, it should be possible for nearly all women with terminal gynaecological cancer to be pain-free. The World Health Organization (WHO) Analgesic Ladder can be effectively utilized for pharmacological treatment of cancer pain. Most side-effects of opioid therapy can be well controlled. Patients whose pain cannot be adequately relieved by systemic opioid therapy may benefit from invasive anaesthetic or neurosurgical techniques. Terminal sedation should be used only after all other therapy has failed. This chapter describes the assessment and management of opioid analgesics and the treatment of their side-effects. Adjuvant analgesic drugs and therapies are also presented.

Spontaneous conception in the presence of stage IIIC endometrioid ovarian cancer.

OBJECTIVE: To describe a rare case of spontaneous conception in a patient with a preexisting metastatic ovarian cancer. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 39-year-old Asian woman who conceived while undergoing an evaluation for primary infertility and newly detected bilateral adnexal masses. INTERVENTION(S): Staging laparotomy and total abdominal hysterectomy and bilateral salpingo-oophorectomy. MAIN OUTCOME MEASURE(S): Anatomic pathology diagnosis. RESULT(S): Blighted ovum and stage IIIC endometrioid adenocarcinoma of ovary. CONCLUSION(S): Metastatic ovarian cancer does not prevent either spontaneous ovulation or spontaneous conception.

A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.

OBJECTIVE: The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. METHODS: Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy. RESULTS: Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). CONCLUSION: The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.

Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.

PURPOSE: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. METHODS AND MATERIALS: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. RESULTS: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. CONCLUSION: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.

Risk of venous access device wound complications in patients undergoing paclitaxel chemotherapy for gynecologic malignancies.

OBJECTIVE: To determine if wound complications after placement of a central venous catheter access device are related to the type of postsurgical cytotoxic chemotherapy administered. METHODS: All patients in a 10-year period undergoing placement of central venous access device followed by postsurgical chemotherapy for gynecologic malignancies were included in this retrospective case-control study. RESULTS: Sixty-eight patients underwent 78 placement procedures followed by chemotherapy. Six catheters (7.7%) in five patients developed wound complications. Variables evaluated included the type of gynecologic malignancy, previous use of chemotherapy, patient age and weight, preoperative white blood cell count, type of access device and insertion site, use of prophylactic antibiotics, type of chemotherapy and interval to administration, development of wound complication, and catheter removal. Univariate analysis shows an association between subsequent catheter site wound complication and paclitaxel use (P = 0.02) as well as wound complication and combined paclitaxel and cisplatin use (P = 0.005). Multivariate analysis with stepwise linear regression confirms that a paclitaxel containing regimen is associated with an increase in wound breakdown (P = 0.04). CONCLUSION: The use of a paclitaxel containing chemotherapeutic regimen administered after placement of an indwelling central venous access device in gynecologic oncology patients is associated with wound complications of the catheter site.

The impact of 2D versus 3D quantitation of tumor bulk determination on current methods of assessing response to treatment.

PURPOSE: Measurements from sequential axial "2D" data in cancer patients are commonly used to assess treatment response or disease progression. This study compares the volume of tumor bulk calculated with 3D reconstructions with that calculated by conventional methods to determine if it might change patient classification. METHOD: All medical, gynecologic, and pediatric oncology patients under treatment who were evaluated with serial CT scans between January 1, 1992, and July 31, 1994, for whom the digital data were available were included in this study. For each tumor site, the maximum diameter and its perpendicular were measured and multiplied together to yield an area. The sum of areas of the measured lesions was used as an approximation of overall 2D tumor volume. In addition, the 2D area of each site was multiplied by its height, yielding a 2D volume. Last, the digital data were loaded into a 3D computer system and total 3D tumor volumes determined. All medical and gynecologic oncology patients were treated based upon the 2D area of tumor. The pediatric oncology patients were treated based upon the 2D volume of tumor measured as per standard practice. The members of each treating oncologic service assessed their patients as to how the other two methods would have changed their classification of the patients' response category. RESULTS: Four hundred thirty-three CT scans were performed in 139 patients, which included 204 baseline and 294 follow-up CT examinations. Seventy patients had new tumor foci and would have been classified as failure by all three methods of tumor bulk measurement. The 3D volume versus the 2D area method of tumor bulk assessment would have changed response categories in 52 of the 294 follow-up CT examinations (p < 0.0001). Thirty-five patients were recategorized from either "no response" to "failure" (21 patients) or "no response" to "response" (14 patients) categories. If only those follow-up studies without new metastatic foci are considered, the 3D volume versus the 2D area methods of tumor assessment would have changed the treatment response category in 23.2%. The use of the 2D volume method of calculating tumor volume of bulk tended to overestimate the overall tumor size by an average of 244 cm3 (p = 0.001). CONCLUSION: The 3D method of tumor volume measurement differs significantly from conventional 2D methods of tumor volume determination. Large prospective studies analyzing the usefulness of 3D tumor volume measurements and assessing possible changes in patient response categories would be required for full utilization of this more accurate method of following disease bulk.

Gestational trophoblastic disease presenting as a large metastasis to the finger.

Cutaneous metastases of gestational trophoblastic disease are extremely uncommon. A patient with metastatic, poor prognosis disease and a large metastatic lesion on her left fifth digit is presented. The clinical course and complete response to EMACO chemotherapy are outlined. The presence of metastatic disease in a reproductive-age woman requires consideration of gestational trophoblastic disease in the differential diagnosis.

Transitional cell bladder carcinoma with presentation mimicking ovarian carcinoma.

In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

Preoperative evaluation of macrophage colony-stimulating factor levels in patients with endometrial cancer.

OBJECTIVE: Our purpose was to examine the relationship between preoperative serum levels of macrophage colony-stimulating factor, alone and in combination with CA 125, and the presence of prognostic clinicopathologic factors and subclinical metastases in women with endometrial cancer. STUDY DESIGN: Ninety-two women who underwent primary exploration for endometrial adenocarcinoma had preoperative serum samples evaluated for macrophage colony-stimulating factor and CA 125 levels. Multivariate analysis was used to determine the associations of surgicopathologic findings with macrophage colony-stimulating factor and CA 125 levels. Logistic regression analysis was used to identify factors associated with the risk of extrauterine disease. The association of macrophage colony-stimulating factor and CA 125 levels with stage, grade, and depth of myometrial invasion and histologic characteristics were analyzed with Fisher's two-tailed exact test. RESULTS: Elevated levels of macrophage colony-stimulating factor were not associated with depth of myometrial invasion, histologic grade, or histologic cell type; however, advanced stage (p = 0.02) and the presence of lymph node metastases (p = 0.04) were associated with elevated levels. Sensitivity and specificity of macrophage colony-stimulating factor for predicting extrauterine disease were 42% and 89%, respectively. If either an elevated macrophage colony-stimulating factor or an elevated CA 125 level was used to predict extrauterine disease, the sensitivity was increased to 67% but the specificity was decreased to 78%. Macrophage colony-stimulating factor elevations predicted lymph node metastases with a sensitivity of 50% and a specificity of 86%. A multivariate regression model showed CA 125 to be the most significant predictor of extrauterine disease; macrophage colony-stimulating factor also contributed prognostic information (p = 0.02). The sensitivity and specificity of the multivariate model for predicting extrauterine disease were 75% and 73%, respectively. CONCLUSION: Macrophage colony-stimulating factor and CA 125 are neither sensitive nor specific enough to be used as predictors of the presence or absence of extrauterine disease in patients with endometrial cancer.

Surgical predictors of para-aortic metastases in early-stage cervical carcinoma.

Radical pelvic surgery for cervical carcinoma is contraindicated in the presence of para-aortic node metastases. However, the incidence of para-aortic nodal involvement is very low in early-stage disease. Therefore, it may not be necessary to subject all patients to para-aortic lymphadenectomy prior to radical hysterectomy. Medical records for 408 patients with early-stage cervical carcinoma treated at the Pennsylvania State University-M.S. Hershey Medical Center were reviewed to ascertain if clinical factors can be utilized intraoperatively to accurately predict those patients at minimal risk for para-aortic lymph node metastases. The presence of clinically suspicious (abnormally enlarged or firm) pelvic or para-aortic lymph nodes or extracervical spread of tumor at the time of exploration were significant predictors of para-aortic metastases (P < 0.001). The majority of patients (85%) had none of these risk factors, and no patient had para-aortic metastases in the absence of these predictors. Suspicious pelvic or para-aortic lymph nodes were present in the minority of patients (15%) and identified all patients with para-aortic metastases. Therefore, para-aortic lymphadenectomy may be safely omitted at the time of exploration for radical hysterectomy in the absence of enlarged or abnormally firm pelvic or para-aortic lymph nodes. In the presence of either of these factors or extracervical spread of disease a para-aortic lymphadenectomy is necessary to rule out metastases.

Staging and recurrence of disease in squamous cell carcinoma of the vulva.

In order to determine the prognostic significance of applying the revised FIGO staging system and identify factors contributing to survival after documentation of recurrent disease, a retrospective chart review of our vulvar cancer population was performed. Over a 17-year interval 135 patients were uniformly treated with primary surgical treatment consisting of radical vulvectomy and bilateral groin dissection. Factors contributing to disease-free survival were analyzed using a Cox proportional hazards model. Covariates of survival after recurrence of disease were analyzed using the log-rank method. Neither the clinical assessment of the groin nodes, nor the presence or absence of perineal involvement were related to outcome. Only lesion size and surgical status of the inguinal nodes were significant predictors of disease-free survival (P = 0.02 and P = 0.03, respectively). In addition, there was a statistically significant relationship between the extent of groin involvement (negative, unilateral positive, and bilateral positive nodes) and associated decrement in disease-free survival (P = 0.01). Thirty patients developed recurrence of disease from 2.0 to 47.3 months following surgery. The location of the recurrence, interval from primary therapy to recurrence, and status of the groin nodes at initial surgery were significant prognostic factors in subsequent survival. The revised staging system demonstrated an improvement in patient stratification compared to the criteria of the prior classification. The data are also consistent with the distinction made between Stage III and IV disease in the new classification. The status of the groin nodes at original surgery remained an important prognostic factor even in those patients who later demonstrated recurrence of disease.

The effect of interinstitution anatomic pathology consultation on patient care.

OBJECTIVE: To determine the effect of routine interinstitution anatomic pathology consultation on patient evaluation and treatment. DESIGN: All interinstitution anatomic pathology consultation diagnoses made during a 1-year period were compared with the original pathologic diagnoses. Patients with discrepant diagnoses were evaluated after an interval of 1 year to determine the correct clinical diagnosis. The relevance of the pathologic consultation to furthering medical evaluation and treatment was determined from a review of the medical record and when necessary from consultation with the patient's physician. SETTING: Patients referred to a university hospital. MAIN OUTCOME MEASURES: We determined the number of patients with discrepant pathologic diagnoses and whether these diagnoses changed the planned surgical procedure, chemotherapy, radiation therapy, or medical evaluation. RESULTS: Seventy-one (9.1%) discrepant diagnoses were identified among the 777 patients. Of these 71 patients, 45 (63%) demonstrated a change in therapy or clinical evaluation as a result of the interinstitution anatomic pathology consultation. In five of these patients the consultation diagnosis was in error. There was a significantly greater percentage of discordant diagnoses among the cytology and fine-needle aspiration biopsies (21%) as compared with the surgical pathology specimens (7.8%; P < .001). CONCLUSIONS: Routine interinstitution anatomic pathology consultation resulted in a change in patient evaluation or treatment in 45 (5.8%) of the 777 cases reviewed. Our interinstitution anatomic pathology consultation policy appears to provide useful diagnostic information, which should contribute to improved patient care. However, when a discrepancy is identified, additional consultation or evaluation should be considered.

Endometrial squamous cell carcinoma following whole pelvic radiation therapy: response to carboplatin.

A case of Stage IV endometrial squamous cell carcinoma occurring 8 years after a low anterior resection and whole pelvic radiation therapy for a Dukes D colon carcinoma is presented. Koilocytosis was present in the tumor. There was no evidence of human papillomavirus antigen or DNA in the tumor. The patient was treated with surgery followed by six cycles of carboplatin chemotherapy. At the completion of chemotherapy there was no clinical or radiological evidence of disease. The tumor recurred 9 months postchemotherapy and the patient died of disease 17 months postdiagnosis.

Preoperative coagulation testing on a gynecologic oncology service.

OBJECTIVE: To determine the prevalence and clinical significance of abnormalities of preoperative coagulation tests in gynecologic oncology patients. METHODS: Three hundred fifty-one patients presenting for inpatient surgical procedures on the gynecologic oncology service at Duke University Medical Center from January 1, 1990 to December 31, 1990, underwent preoperative coagulation testing. Twenty-nine patients had only prothrombin time (PT) and partial thromboplastin time (PTT) measured; the remaining 322 had preoperative measurement of PT, PTT, fibrinogen, and fragment D-dimer. Outcomes assessed were perioperative hemorrhage resulting in death or reoperation, postoperative hematomas, and need for intraoperative and postoperative transfusion. RESULTS: Twelve of 351 patients (3.4%) had abnormally elevated PT or PTT; six of these were attributable to risk factors unrelated to malignancy. One hundred fifty-six of 322 subjects (48.4%) had abnormal levels of fibrinogen, mostly elevations above 360 mg/dL, and 88 of 322 subjects (27.3%) had positive tests for D-dimer. Fifty-seven (17.7%) had both elevated fibrinogen and positive D-dimer. One hundred eighty-eight of 322 subjects had at least one abnormal test result. There were no perioperative deaths or reexplorations because of hemorrhage. There was one postoperative hematoma. The combination of an elevated fibrinogen and a positive D-dimer test was a significant predictor of perioperative transfusion in a logistic regression model incorporating stage, preoperative hematocrit, and age (odds ratio 1.96, 95% confidence interval 1.03-3.76). However, the attributable risk associated with this abnormality was only 7.7% in patients at highest risk of transfusion. CONCLUSION: Although abnormalities in coagulation are common in patients undergoing surgery for gynecologic malignancy, preoperative testing for occult coagulopathy provides little clinically useful information.

Tissue distribution of TAG-72 in malignant mixed müllerian tumors of the uterus.

Malignant mixed müllerian tumors are the most frequent sarcomas arising from the uterus. Since these tumors are traditionally associated with a poor prognosis, tumor-associated antigens may be useful in the evaluation and follow-up of affected patients. The purpose of this study was to determine the frequency and tissue distribution of TAG-72, an antigen frequently expressed in endometrial carcinomas, and to compare it to CA 125 and CA 19-9 expression in malignant mixed müllerian tumors of the uterus. Consecutive, paraffin-embedded sections from 35 tumors were immunohistochemically evaluated using primary antibodies directed against the tumor-associated antigens. These antigens were demonstrated in the neoplastic glandular epithelium and not in the sarcomatous portion of the tumor. The degree of antigen expression was unrelated to the nature of the sarcomatous element present (homologous vs heterologous). Positive staining (> or = 5% of the glandular epithelium) for TAG-72 was present in 66% of the tumors; another 6% of the tumors contained focal staining (< 5% of the glandular epithelium) for TAG-72. Although cytoplasmic and intraluminal staining were present, cell surface staining was the most prominent feature of TAG-72 expression. Tumors were more likely to be positive for TAG-72 than either CA 125 (P = 0.046) or CA 19.9 (P = 0.004). The extent of TAG-72 expression was unrelated to the extent of disease (intrauterine vs extrauterine) and overall patient survival. However, antigen expression was correlated with the differentiation of the glandular component present.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of superficial wound separation with subcutaneous retention sutures.

The objective of this prospective study was to determine the efficacy of subcutaneous retention sutures in the prevention of superficial wound separation in obese women undergoing gynecologic surgery. From 1985 to 1990, 80 women with subcutaneous tissue of 5 cm or greater undergoing laparotomy were randomly assigned to either standard wound closure (37 patients) or closure including subcutaneous retention sutures (43 patients). We examined the relationship of the following factors to the development of superficial wound dehiscence: malnutrition (total protein < 6.0 mg/dl, albumin < 3.0 mg/dl), minidose heparin (5000 U subcutaneously every 8 hr for 5 days), diabetes mellitus, prolonged operative time (> 180 min), intraoperative spillage of enteral contents, and subcutaneous retention sutures. In a univariate analysis, malnutrition (P = 0.02), the use of heparin (P = 0.03), and the absence of retention sutures (P = 0.02) were associated with an increased risk of separation. In a multivariate analysis, malnutrition (P = 0.02), low-dose heparin (P = 0.03), and the absence of retention sutures (P = 0.04) retained their independent association with superficial wound separation. This study suggests that the use of subcutaneous retention sutures reduces the incidence of superficial wound separation in obese women undergoing gynecologic surgery.

Constitutive production of macrophage colony-stimulating factor and interleukin-6 by human ovarian surface epithelial cells.

Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal epithelial cells from which epithelial ovarian neoplasms are thought to arise. Epithelial cells from the surface of premenopausal human ovaries were established in short-term cultures. The cells bound anti-cytokeratin antibodies and exhibited characteristic epithelial morphology by light and transmission electron microscopy. M-CSF and IL-6 were detected in supernatants from cultures of these cells, using assays specific for each factor. Cytokine levels were comparable to those in supernatants from ovarian and breast cancer cell lines. M-CSF expression could also be demonstrated by immunohistochemical analysis with specific rabbit heteroantiserum. Thus, M-CSF and IL-6 are produced constitutively by normal as well as by neoplastic ovarian epithelium.

Tissue CA 125 and CA 19-9 in malignant, mixed mesodermal tumors of the uterus.

Mixed mesodermal tumors of the uterus are biphasic neoplasms composed of both a malignant epithelium and a sarcomatous stromal component. Elevated levels of tumor-associated antigens, such as CA 125, have been reported in some patients with these tumors. The purpose of this study was to determine the frequency and tissue distribution of CA 125 and CA 19-9 in malignant mixed mesodermal tumors of the uterus treated with primary surgery. Consecutive, paraffin-embedded sections from 35 tumors were immunohistochemically evaluated using primary antibodies directed against CA 125 and CA 19-9. CA 125 and CA 19-9 were demonstrated in the neoplastic glandular epithelium and not in the sarcomatous portion of the tumor. The localization of CA 125 and CA 19-9 suggested that both antigens were epithelial secretory products. Positive staining (> or = 5% of the glandular epithelium) for CA 125 was present in 46% of the tumors; another 14% of the tumors contained focal staining (< 5% of the glandular epithelium) for CA 125. Positive staining for CA 19-9 was demonstrated in 34% of tumors; another 17% contained focal staining for CA 19-9. The markers were concordant in 77% of the tumors examined. Antigen expression was unrelated to the nature of the sarcomatous element (homologous vs heterologous), the extent of disease, and patient survival. However, the epithelial component of these sarcomas frequently expressed these antigens and the degree of expression was related to the cell type and the histologic grade of the glandular element.