Cystoscopy after computed tomography scan to identify bladder invasion in cervical cancer.

OBJECTIVE: To determine the clinical utility of cystoscopy to rule out bladder invasion in cervical cancer patients who have had pelvic computed tomographic (CT) scan. METHODS: We reviewed charts of 49 patients at Walter Reed and Tripler Army Medical Centers who had International Federation of Gynecology and Obstetrics stage II or greater cervical cancer and who underwent both cystoscopy and CT scan before treatment. Data retrieved included diagnosis, race, age, cystoscopy results, and CT scan reports. These patients were evaluated and treated between January 1, 1991, and September 1997. RESULTS: The mean age of the patients was 50 years. Seven of the women were Asian, five black, six white, one Hispanic, and 30 Pacific Islander. There were 40 squamous cell carcinomas and nine adenocarcinomas. There were 25 stage II, 20 stage III, three stage IV, and one recurrent stage II carcinomas. Three patients with bladder invasion were identified by cystoscopy and all also were identified with possible bladder invasion by CT scan. Two additional cases of possible invasion seen on CT scan proved not to be invasion with cystoscopy. The positive predictive valve of CT scan in predicting bladder invasion was 60% (three of five). The negative predictive valve of CT scan in predicting bladder invasion was 100%. CONCLUSION: The utility of performing cystoscopy to rule out bladder invasion in a patient with no evidence of bladder involvement on CT scan is low and might not be necessary.

Alpha-1 acid glycoprotein is an immunosuppressive factor found in ascites from ovaria carcinoma.

BACKGROUND: Although the ascites of patients with ovarian carcinoma has been reported to contain immunosuppressive factors, the identity and source of this activity has not been fully elucidated. The objective of this study was to describe the purification of a single immunosuppressive protein, alpha-1 acid glycoprotein, from ovarian carcinoma ascites, identify its site of production, and describe a possible mechanism by which it inhibits lymphocytes. METHODS: Ascites from proteins from five patients with epithelial ovarian carcinoma first were differentially precipitated by size with different concentrations of polyethylene glycol and then separated on the basis of isoelectric focusing. The protein factions then were placed in a lymphocyte proliferation assay to determine immunosuppressive activity. Western blot analysis was used to identify alpha-1 acid glycoprotein as an immunosuppressive protein in ascites. Total RNA was extracted from ovarian and hepatic cell lines as well as primary and recurrent ovarian tumor samples. Reverse-transcriptase polymerase chain reaction then was utilized to identify the site of production of this protein. Purified alpha-1 acid glycoprotein was placed in lymphocyte culture and its effects on lymphocyte interleukin-2 (IL-2) production were measured by enzyme-linked immunoadsorbent assay. RESULTS: Addition of purified alpha-1 acid glycoprotein to the lymphocyte assay resulted in a 60% decrease in lymphocyte proliferation (P < 0.05). Alpha-1 acid glycoprotein transcript was not identified in ovarian tumor cells. The addition of purified alpha-1 acid glycoprotein to the lymphocyte culture resulted in a 65% decrease in IL-2 secretion into the media (P < 0.05). CONCLUSIONS: Alpha-1 acid glycoprotein is an immunosuppressive protein purified from ovarian carcinoma ascites. It is not expressed primarily by ovarian carcinoma cells. It appears to inhibit IL-2 secretion by lymphocytes.

The in vitro effect on T cell function of soluble IL-2Ralpha from advanced ovarian cancer ascites.

Activated T cells not only secrete interleukin-2 (IL-2) and express cell surface interleukin 2 receptor alpha (IL-2R alpha), but also shed IL-2R alpha. This soluble receptor is a truncated form of the membrane-bound p55 receptor with a similar binding affinity. It has been proposed that soluble IL-2R alpha (sIL-2R alpha) could negatively modulate local immune response. High levels of sIL-2R alpha have been found in the serum and ascites of ovarian cancer patients. The purpose of this investigation is to determine the amount of in vitro T cell inhibition seen in ovarian cancer ascites that is attributable to high levels of sIL-2R alpha. Purified sIL-2R alpha at levels up to 100,000 pg/ml was placed in lymphocyte proliferation assays. Soluble IL-2R alpha was removed from the ascites of three patients with advanced ovarian cancer. Lymphocyte proliferation assays utilizing phytohemaglutin (PHA) stimulation were carried out with this ascites. Untreated ascites from each patient served as control. Addition of purified sIL-2R alpha to lymphocyte proliferation assays failed to demonstrate significant lymphocyte suppression. Addition of ascites to the lymphocyte assays resulted in up to an 80% decrease in lymphocyte proliferation. Neutralization of ascites sIL-2R alpha as well as removal of sIL-2R alpha via a protein G column failed to reverse any of the observed lymphocyte suppression. We conclude that although sIL2R alpha is elevated in ascites of patients with ovarian cancer, it does not account for the profound ascites-induced T cell suppression observed in vitro.

Major basic protein as a marker of malignant potential in trophoblastic neoplasia.

OBJECTIVE: We tested whether serum pregnancy-associated major basic protein levels distinguish between benign and malignant trophoblastic disease. STUDY DESIGN: We compared serum pregnancy-associated major basic protein levels in seven patient groups: nonpregnant and pregnant controls, partial moles, complete moles, persistent moles, placental-site trophoblastic tumors, and choriocarcinoma. RESULTS: The results showed that patients with partial and complete moles had elevated serum pregnancy-associated major basic protein levels comparable to normal pregnancy. In contrast, patients with persistent mole, placental-site trophoblastic tumors and choriocarcinoma had low median serum levels comparable to those of the nonpregnant controls. Significant differences were shown between the complete and persistent mole groups (p = 0.0001) and between the complete mole group and the choriocarcinoma group (p = 0.0001); however, persistent moles were indistinguishable from choriocarcinoma (p = 0.2010). CONCLUSION: Serum pregnancy-associated major basic protein levels thus distinguish between benign disorders, such as pregnancy and partial and complete moles, and trophoblastic tumors, such as persistent moles and choriocarcinoma. The absence of elevated serum levels of pregnancy-associated major basic protein may be useful clinically to indicate a more aggressive or frankly malignant tumor.

Comparison of probe sheaths for endovaginal sonography.

OBJECTIVE: To compare the effectiveness of commercially available probe covers with less expensive condoms. METHODS: During a 10-month period, sonographers performed endovaginal ultrasound examinations on patients by randomly testing either commercially available probe covers or condoms on the vaginal probe. After use, the sheaths were tested for damage by filling them with water to observe for leakage and thereby determine the breakage rate. RESULTS: Perforations were noted in 15 of 180 probe covers and three of 180 condoms (8.3 versus 1.7%, P < .05; relative risk [RR] 5.4, 95% confidence interval [CI] 1.4-18.5). Potential contamination of the endovaginal probe occurred during nine of 174 examinations and one of 178 examinations in which probe covers and condoms, respectively, were used (P < .05; RR 9.7, 95% CI 1.2-67.7). CONCLUSION: Condoms are less expensive and superior to commercially available probe covers for covering the ultrasound probe during endovaginal examinations.

Laparoscopic lymph node dissection in the evaluation and management of patients with pelvic malignancy.

OBJECTIVE: This retrospective investigation describes our experience with laparoscopic pelvic and paraaortic lymph node dissection at a military medical center. METHODS: The charts of all patients undergoing laparoscopic pelvic and paraaortic lymph node dissection between July 1992 and May 1994 were reviewed for age, weight, cancer type, tumor stage, operative procedures, estimated blood loss, complications, number and pathologic results of lymph nodes removed, preoperative computed tomography findings, and postoperative therapy. RESULTS: The study group was composed of 20 patients, of which 15 had cervical cancer, 2 had ovarian cancer, and the rest had other pelvic malignancies. The mean age was 46 years old, with a mean weight of 155 pounds. The average number of lymph nodes removed was 26, with 9 of the 20 patients having positive nodes. Only one patient had preoperative radiographic evidence of lymphadenopathy. Mean estimated blood loss was 224 cc. Four patients required open procedures, two for bleeding during the laparoscopic node dissection and two who were unable to be completed through the laparoscope for technical reasons. Radical hysterectomy was avoided in two of the studied patients after finding positive lymph nodes. We conclude that in a military medical center, laparoscopic pelvic and paraaortic lymph node dissection in patients with certain pelvic malignancies is feasible and helps guide the management of these patients.

Squamous cell carcinoma of the ovary.

Benign cystic teratoma is a very common ovarian lesion; and it commonly occurs during a woman's reproductive years and most often is benign. In approximately 1% to 2% of cases, however, it can undergo a malignant transformation with a very poor prognosis. This is especially the case when disseminated disease is present. Usually the associated malignancy is squamous cell carcinoma, and radical surgery is recommended. An American Samoan woman was air-evacuated to Tripler Army Medical Center for further evaluation and therapy after having undergone an exploratory laparotomy and right ovarian cystectomy. Her pathology at the time of her initial procedure revealed a mature cystic teratoma with a malignant degenerative component. Her diagnostic evaluation upon arrival was unremarkable except for her physical exam and pelvic CT. She subsequently underwent a radical surgical procedure to include a surgical staging procedure, revealing disseminated squamous cell carcinoma with FIGO stage III disease. Whereas malignant transformation of a benign cystic teratoma is a rare occurrence, a high index of suspicion should be maintained whenever a preoperative diagnosis is encountered; a radical surgical approach with en bloc resection should be employed. Adjuvant therapy with radiation or chemotherapeutic agents in general has not been shown to improve the outcome, especially in disseminated disease.

Tuberculous peritonitis in a young female diagnosed using mini-laparotomy: a case report.

An 18-year-old female Pacific Islander with abdominal pain, ascites, and fever was transferred to our hospital with suspected ovarian malignancy. These nonspecific clinical features of tuberculous peritonitis in a female frequently contribute to misdiagnosis. Preoperative findings included negative sputums, negative purified protein derivative, and no acid-fast bacilli (AFB) found in peritoneal fluid or fine needle biopsy of the omentum. Tuberculous peritonitis was diagnosed after omental biopsy obtained at mini-laparotomy showed granulomatous inflammation and positive isolation of AFB.

Infectious morbidity after radical vulvectomy.

OBJECTIVE: This retrospective investigation describes the infectious morbidity of patients following radical vulvectomy with or without inguinal lymph node dissection. METHODS: The charts of patients undergoing radical vulvectomy between January 1, 1986, and September 1, 1989, were reviewed for age, weight, cancer type, tumor stage, operative procedure(s), prophylactic antibiotic and its length of use, febrile morbidity, infection site, culture results, significant medical history, and length of use and number of drains or catheters used. RESULTS: The study group was composed of 61 patients, 14 of whom underwent a radical vulvectomy and 47 who also had inguinal lymph node dissection performed. Twenty-nine patients (48%) had at least 1 postoperative infection. Five patients (8%) had 2 or more postoperative infections. The site and incidence of the infections were as follows: urinary tract 23%, wound 23%, lymphocyst 3%, lymphatics (lymphangitis) 5%, and bowel (pseudomembranous colitis) 3%. The most common pathogens isolated from both urine and wound sites were Pseudomonas aeruginosa, enterococcus, and Escherichia coli. A significant decrease in wound infection was demonstrated when separate incisions were made for inguinal lymph node dissection (P <0.05). The mean number of days to onset of postoperative infection for wound, urine, lymphatics, lymphocyst, and bowel were 11, 8, 57, 48, and 5, respectively. CONCLUSIONS: We conclude that the clinical appearance of post-radical vulvectomy infections is delayed when compared with other post-surgical wound infections. Second, utilizing separate inguinal surgical incisions may reduce infectious morbidity. Finally, tumor stage and type do not necessarily increase the infectious morbidity of radical vulvar surgery.

Ascites levels of haptoglobin in patients with ovarian cancer.

BACKGROUND: Haptoglobin is an acute-phase reactant protein involved in immune regulation. It has been isolated from malignant ovarian ascites and has been shown to be capable of mediating nonspecific immune suppression in vitro in humans and in vivo in experimental animals. The range of concentrations under which such a nonspecific suppression is observed lies well within concentrations of haptoglobin observed in vivo. This immune suppression could adversely affect patient outcome. METHODS: Based on this information, ascites haptoglobin levels of 21 consecutive patients with ovarian cancer who underwent initial surgical debulking were determined. After the patients received chemotherapy, they were divided into those having a positive and those have a negative second-look operation. RESULTS: Seventeen patients with positive pathology at second look had an initial mean ascites haptoglobin level of 99 +/- 49 mg/dl. The mean haptoglobin level in the four patients with negative findings was 67 +/- 42 mg/dl. The difference in these mean haptoglobin levels is not statistically significant (P > 0.05). CONCLUSION: Although the number of patients in this study is small, the wide range of values documented in both groups make it doubtful that an initial absolute ascites haptoglobin level will prove clinically prognostic of eventual disease status at the time of second look laparotomy.

Serum levels of macrophage colony-stimulating factor in patients with ovarian cancer undergoing second-look laparotomy.

OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of macrophage colony-stimulating factor serum levels in patients with ovarian cancer undergoing second-look laparotomy. STUDY DESIGN: The presurgical serum levels of macrophage colony-stimulating factor from 33 consecutive patients with ovarian cancer undergoing second-look laparotomy were determined and compared with those of 50 healthy control subjects. Mean differences in groups were evaluated with the Student t test. RESULTS: Sixteen of 33 patients had a positive result at second look and a mean serum macrophage colony-stimulating factor level of 2.31 +/- 1.45 ng/ml. Seventeen of 33 patients had a negative result at second look and a mean macrophage colony-stimulating factor level of 1.90 +/- 0.86 ng/ml (p greater than 0.05). The mean macrophage colony-stimulating factor level in the control group was 1.20 +/- 0.51 ng/ml. This was statistically lower than the mean level found in patients with a negative second-look result (p less than 0.05). CONCLUSION: Regardless of tumor status, serum macrophage colony-stimulating factor levels tend to be elevated at the time of second-look laparotomy.

Marker rhythmometry with macrophage-colony stimulating factor (M-CSF).

In a patient with a debulked müllerian adenocarcinoma involving the ovary, an elevated serum concentration of macrophage-colony stimulating factor (M-CSF) (5.3 ng/ml) was lowered into the range of the age- and gender-matched controls by a 24-hour infusion of 135 mg/m2 of taxol, as was a Ca125 of 1480 U/ml by three such taxol courses given at 3-week intervals (to 14 U/ml). A downward trend of M-CSF in serum with an about-14-hour ultradian modulation during the first chemotherapy course resembles that of the concomitantly assessed Ca125. A decreasing trend modulated by an about-half-weekly component is found in M-CSF of fractionated urines collected at spontaneous voidings around the clock for 5 days. M-CSF may serve as a chronobiologic marker for optimizing, on an individualized basis, 1) the infradian scheduling of chemotherapy courses and 2) the ultradian-circadian within-course time patterns. Timing based on markers of the anticancer effect aims at teh as-yet unattained transfer from rodent to human of cancer cures that were not previously feasible without chronobiologic considerations. This goal can be pursued with M-CSF as well as Ca125 and UGP as possibly complementary chronobiologic markers in a chronotherapy trial with taxol in humans.

Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells.

Monoclonal antibodies which bind selectively to cancer cells are currently used for tumor localization and for targeting cytotoxic reagents. The success of these approaches depends on the specificity of the antibody and its reactivity to a majority of the tumor samples. Frequently, monoclonal antibodies are generated by immunizing mice with antigenic preparations from a single tumor cell line. Antibodies generated under these conditions often react to a narrow range of tumors. In the present study, mice were immunized with multiple ovarian cancer cell lines in a sequential manner to amplify the immune response against common antigenic determinants expressed in these cell lines. Spleen cells from the immunized mice were then fused with NS-1 myeloma cells to establish hybridomas. Two cell lines were selected on the basis of their selective reactivity to ovarian cancer cells after extensive screening. Monoclonal antibodies OVX1 and OVX2 bound to all 5 ovarian carcinoma cell lines tested and did not bind to normal fibroblast cells. These antibodies recognized a unique antigenic determinant present in ovarian and breast cancer cells. Cross-blocking studies showed that the binding of OVX1 and OVX2 is not displaceable by 10 other previously described anti-ovarian antibodies including OC125. In immunocytochemical studies, OVX1 reacted to a majority of ovarian cancer tissues (17 of 20) and did not bind to normal ovarian tissues. Preliminary results indicate that OVX1 and OVX2 antibodies are directed to a high molecular weight antigen. These antibodies could be used in the preparation of cytotoxic conjugates.

Pseudomyxoma peritonei--experience from a tertiary referral centre.

Pseudomyxoma peritonei is a clinical diagnosis of massive abdominal swelling by a gelatinous material, produced usually from an ovarian or appendiceal primary. It is a rare entity that is usually histologically benign but behaves clinically in a malignant fashion with recurrent growth, although not demonstrating histological stromal invasion. The disease remains localized to the peritoneal cavity and the clinical course is one of repeated episodes of intestinal obstruction caused by extrinsic compression that seem only to be relieved by surgical debulking. Variable responses have been obtained with adjuvant chemo-, radio- and immunotherapy, but these isolated responses are unable to be reproduced and so there is no accepted adjuvant treatment for this disease.

Fatal Yersinia enterocolitica (serotype 0:5,27) sepsis after blood transfusion.

Septicemia is a rare complication of blood transfusion. This is probably primarily due to the use of sealed disposable containers for blood collection and the storage of red cell-containing components at 4 degrees C. However, despite these measures, septicemia due to blood transfusion continues to occur. We report here a fatal case of Yersinia enterocolitica septicemia due to a contaminated unit of red cells which was collected from an apparently healthy, asymptomatic blood donor. The organism grows at cold temperature and multiplies during storage of red blood cell-containing components. Contaminated components do not show any visible abnormalities. The possibility of transfusion-transmitted Y. enterocolitica should be considered in patients who have symptoms of sepsis or shock following transfusion.

Evaluation of subclavian catheters in gynecologic cancer patients.

Sixty-eight semipermanent subclavian catheters were placed in 61 patients with gynecologic malignancies. The principal indicator for placement was chemotherapeutic administration. Other uses included blood transfusion, antibiotic infusion, and hyperalimentation. The minor complication rate of 21% included exit site infections and clotted, broken, and dislodged catheters. There were no acute surgical complications; i.e., bleeding or pneumothorax, but there was a 6% major complication rate, which included four cases of sepsis and a case of a broken intravascular catheter.