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Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

Aged↗

Gemcitabine associated vasculitis leading to necrotizing enterocolitis and death in women undergoing primary treatment for epithelial ovarian/peritoneal cancer.

We present two patients who developed necrotizing enterocolitis following their first cycle of chemotherapy for epithelial ovarian/peritoneal cancer. After optimal cytoreductive surgery, both women received gemcitabine as part of a chemotherapy protocol. One patient developed necrotizing enterocolitis, 1 day after chemotherapy and the other 8 days after chemotherapy. The first patient succumbed to the enterocolitis despite aggressive supportive care. The second patient succumbed despite both aggressive supportive care and surgical intervention. Pathologic review for both patients revealed a drug induced vasculitis causing necrotizing enterocolitis.

Aged↗

Use of tamoxifen in asymptomatic patients with recurrent small-volume ovarian cancer.

OBJECTIVES: Tamoxifen, a well-tolerated oral hormonal agent with biological activity in ovarian cancer, is a potentially attractive option in asymptomatic patients with recurrent disease. Unfortunately, the clinical utility of the drug in this specific setting has not been well documented. PATIENTS AND METHODS: A retrospective review was conducted of patients with cancers of the ovary, fallopian tube, and primary cancer of the peritoneum at the Cleveland Clinic who experienced recurrence of the malignancy, in the absence of large volume disease (by physical exam and radiographic evaluation) or any cancer-related symptoms, and who received tamoxifen (20 mg [most patients] or 40 mg/day) before re-initiation of cytotoxic chemotherapy. RESULTS: Fifty-six patients (45 after primary chemotherapy; 12 after second-line treatment) satisfied the criteria noted above. The median duration of treatment was 3 months (range 1-30 months), with 42% and 19% of patients remaining on tamoxifen for >/=6 and >/=12 months, respectively. Reasons for discontinuation were equally divided between three causes: (a) continued rise in CA-125 antigen level without symptoms or other objective signs of cancer; (b) evidence of progressive disease by physical exam or radiographic evaluation in the absence of symptoms; and (c) development of cancer-related symptoms. CONCLUSION: In the absence of data from a randomized controlled trial which defines optimal management of the asymptomatic ovarian cancer patient with documented recurrent disease, tamoxifen is a rational management option, although it remains unknown if the delay in subsequent administration of chemotherapy in some individuals for periods greater than 6-12 months results from a direct effect of this agent or simply reflects the natural history of disease in a subset of patients in this clinical setting.

Adult↗

Phase 2 trial of carboplatin plus tamoxifen in platinum-resistant ovarian cancer and primary carcinoma of the peritoneum.

OBJECTIVES: A previously reported phase 2 trial suggested substantial clinical activity associated with the combination of a platinum agent and tamoxifen in the treatment of platinum-resistant ovarian cancer. We wished to confirm or refute this observation in a patient population with well-characterized platinum-resistant disease. METHODS: Patients with ovarian or fallopian tube cancers or primary carcinoma of the peritoneum whose disease had either failed to respond to a platinum-based regimen or had responded but experienced a "treatment-free interval (TFI)" of < or =3 months, or if the TFI was >3 months they had been retreated and failed a platinum-based program, were eligible for entry into this phase 2 single institution protocol. Carboplatin (AUC 5) was delivered on a q-21 day cycle. Tamoxifen was administered at a dose of 80 mg/day for the first cycle, and then reduced to 40 mg/day. Treatment was to be continued until evidence of disease progression or unacceptable toxicity. RESULTS: Fourteen patients were treated on this phase 2 trial. In addition to being platinum-resistant, 10 patients had cancers that were also documented to be taxane-resistant (similar criteria to that defined above for platinum). While treatment was generally well tolerated, there were no objective (measurable disease or CA-125 response criteria) or subjective responses to this treatment program. CONCLUSION: In this phase 2 trial, we have been unable to confirm a meaningful level of clinical activity for the combination of carboplatin plus tamoxifen in a patient population with well-characterized platinum-resistant ovarian cancer.

Adult↗

Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions.

OBJECTIVES: The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR. METHODS: We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6-h, 12-step desensitization protocol with a 30-min premedication regimen. Skin tests were performed on five patients. RESULTS: Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re-administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. CONCLUSION: The 6-h, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen-specific mast cell desensitization.

Adult↗

Meigs syndrome and gliomatosis peritonei: a case report and review of literature.

To the best of our knowledge, pseudo-Meigs syndrome (PMS) has never been described in the setting of gliomatosis peritonei (GP), both arising from an ovarian teratoma. We present a case of ovarian teratoma with both these rare findings. The case is unique as it presents two rare manifestations of ovarian teratoma in the same patient; there are many cases in the literature where both these manifestations have been described in different patients. The case is also rare because lymph node involvement along with gliomatosis was found. We review the literature for these two rare complications of ovarian teratoma.

Adult↗

Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer.

OBJECTIVES: The identification of proteins that are selectively expressed in cancer and with potential to elicit an immune response is the first step towards antigen-specific immunotherapy. The Wilms tumor gene product (WT1) is inherently immunogenic and is now thought to be oncogenic. The aim of this study was to determine the expression of WT1 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics. METHODS: WT1 expression was examined using immunohistochemistry applied on a tissue microarray of normal tissues and a panel of 100 EOC tissues. The distribution of WT1 expression and clinico-pathologic variables were analyzed. Survival probabilities were estimated by Kaplan-Meier method, and statistical significance was determined by the log-rank test. RESULTS: WT1 expression was observed in 78/100 of specimens. The predominant expression pattern was homogenous, occurring in 66/100 (66%) of WT1-positive specimens, while 12/100 (12%) demonstrated heterogeneous staining. In normal tissues, WT1 expression was noted in kidneys, splenic capsule, Sertoli cells of the testis, and granulosa cells of the ovary. The median follow-up of the patient population was 30 months. Patients with WT1-positive tumors tended to have a higher grade (P = 0.006) and stage (P = 0.002) of tumor. However, there were no significant differences in the distribution of patients with WT1-positive tumors in relation to disease-free and overall survival. CONCLUSIONS: Our data demonstrate that WT1 is expressed at high frequency in patients with EOC. Since WT1 demonstrates tissue-restricted expression and is inherently immunogenic, it could represent an attractive target for antigen-specific immunotherapy in EOC.

Adult↗

Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature.

UNLABELLED: Endometrial stromal sarcoma (ESS) is a rare disease with probably less than 700 new cases in the US or EU per year. ESS usually expresses steroidal receptors and is regarded to be hormone-sensitive. A higher risk in women receiving estrogen replacement therapy (ERT) or tamoxifen has been suspected, and remissions following treatment with progestins have been reported in case studies. Aromatase inhibitors represent an interesting new treatment option. Due to the rarity of the tumor, only few case series and no prospective studies are published. We therefore conducted a retrospective study to evaluate the influence of hormonal treatment to ESS. METHODS: Our institutional sarcoma data bank was screened for cases of ESS since 1999. All corresponding files and radiographs were reviewed retrospectively. RESULTS: Ten patients with low-grade ESS were identified. Diagnosis was established before or by hysterectomy in 6 patients, by local recurrence after previous hysterectomy for nonmalignant disease in 3 patients or by pulmonary metastases with no primary tumor found so far in 1 patient. 5/10 patients were on ERT and 3/10 on tamoxifen at the time of diagnosis of metastatic disease. Treatment strategies consisted of stopping ERT and tamoxifen, respectively, or initiation of the progestin MPA or letrozole. Three patients achieved stable disease after stopping ERT. 2/3 patients responded to MPA as first-line treatment (1 CR; 50+ months, 1 PR; 9 months). 4/5 patients responded to letrozole as first-line therapy (3 PR;3+, 9+ and 10+ months) or second-line treatment after MPA (1 PR; 37+ months). 9/10 patients are alive 33 to 255 months after hysterectomy. Survival since diagnosis of metastatic disease is 4 to 164 months. CONCLUSIONS: Patients with a previous history of low-grade ESS should not be treated with estrogens or tamoxifen. If nevertheless present, withdrawal of ERT or tamoxifen is strongly advised, resulting in disease stabilization in some cases. MPA and letrozole, in particular, are highly effective and lead to sustained disease control in most cases.

Adult↗

Testing of two binary grading systems for FIGO stage III serous carcinoma of the ovary and peritoneum.

OBJECTIVE: A variety of histologic grading systems for ovarian carcinoma have been used, but there is no widely accepted system. Binary grading systems are inherently superior to the more common three-grade systems because they are more reproducible and they correspond to the number of options in the binary treatment decision for which grade is considered important: the use of or withholding of chemotherapy. METHODS: One hundred thirteen unselected FIGO stage III serous carcinomas of the ovary and peritoneum were tested with two grading systems: a binary system recently proposed by investigators at MD Anderson Cancer Center (MDACC) and a new binary system we formulated at the Washington Hospital Center (WHC). Both of these systems are based on nuclear grade. The WHC system has a higher threshold of nuclear size for diagnosing high-grade tumors. RESULTS: The WHC system separated the cases into 89 high-grade and 24 low-grade tumors. The median survival rates were 30 and 49 months for high and low grade respectively, and the actuarial survival curves were not significantly different (P > 0.10). The MDACC system separated the cases into 103 high-grade and 10 low-grade tumors. With this system, low-grade tumors were significantly more likely than high grade to be stage IIIA (P < 0.05) and occurred at a mean age of 57 years compared to 65 years for high-grade tumors (P < 0.05). Low-grade tumors were suboptimally debulked in 10% of cases compared to 27% for high-grade tumors (P > 0.05). The median survival for high-grade tumors was 34 months, and the median for low grade has not been reached. The actuarial survival curves were not significantly different (P = 0.065). CONCLUSION: The MDACC grading system appears more promising than the WHC system. The MDACC system separates a small (9% of advanced stage serous carcinomas) but distinctive well-differentiated tumor which usually has the appearance of invasive low-grade (micropapillary) serous carcinoma. The rarity of this tumor, however, will require a larger series to demonstrate prognostic value. The WHC system, which was designed to enlarge the low-grade group to a size that would be more meaningful in clinical practice, did not demonstrate a survival difference. The failure of the WHC system suggests that attempts to enlarge the low-grade group using histologic features alone are unlikely to be successful. The potential for confounding of grade with substage, volume of residual disease and patient age are issues that may impede determination of the independence of tumor grade in prognosis, and more data, especially for low-grade tumors, are needed.

Cystadenocarcinoma, Serous↗

Reduction of the intraperitoneal inflammation associated with endometriosis by treatment with medroxyprogesterone acetate.

An intraperitoneal inflammatory exudate has been repeatedly observed in infertile women without mechanical compromise of the pelvic viscera, particularly with endometriosis. This is manifested by increases in the peritoneal fluid volume, leukocyte number, and proteolytic enzyme concentrations. We tested the hypothesis that the stimulus responsible for eliciting this intraperitoneal inflammation is retrograde menstruation by measuring the peritoneal fluid volume and leukocyte count in 16 infertile women with endometriosis before and after ovulation suppression with medroxyprogesterone acetate, 30 mg/day for 4 months. Medroxyprogesterone acetate therapy significantly reduced the peritoneal fluid volume (22.5 +/- 4.1 versus 6.8 +/- 0.9 ml mean +/- SE, p less than 0.0001), the peritoneal fluid leukocyte count (30.7 +/- 6.5 versus 7.1 +/- 0.7 x 10(6) cells per patient, p less than 0.0001), and American Fertility Society score (23.2 +/- 5.1 versus 15.4 +/- 4.1, p less than 0.0002). We conclude that medroxyprogesterone acetate treatment reduces the intraperitoneal exudate associated with endometriosis. These results support the contention that the stimulus eliciting the intraperitoneal inflammation in infertile women with endometriosis is retrograde menstruation.

Adult↗

Field cancerization: why late "recurrent" ovarian cancer is not recurrent.

OBJECTIVE: Late "recurrence" of ovarian cancer may result from either regrowth of dormant tumor cells or from development of a new cancer caused by the phenomenon of field cancerization. Clinically, some recurrent ovarian cancers show the same therapeutic sensitivities to chemotherapy and surgery as did the primary disease, whereas others are refractory to all therapy. We hypothesize that recurrent ovarian cancers are distinguishable on the basis of a molecular genetic fingerprint and that some are actually new primary cancers of the peritoneum rather than recurrent ovarian cancer. STUDY DESIGN: We constructed molecular genetic fingerprints of 13 paired primary and late recurrent ovarian cancers to study their clonal relationships. The tumor pairs were analyzed for p53 mutations and allelotypes, patterns of X-chromosome inactivation, loss of heterozygosity, and microsatellite instability at 12 different loci on 6 different chromosomes. Techniques used included single-strand conformational polymorphism mutation screening and polymerase chain reaction-based sequence analysis of the p53 locus, restriction digestion of the androgen receptor locus to determine X-chromosome inactivation, and polyacrylamide gel electrophoresis of highly polymorphic dinucleotide, trinucleotide, and tetranucleotide repeats. RESULTS: The average age at initial diagnosis for this cohort was 54.7 years (range 45.3 to 65.5). Mean interval to recurrence was 42.7 months (range 28 to 62). Molecular fingerprints were characterized for 4 to 8 informative loci per tumor pair. The fingerprints of 10 (77%) differed significantly, strongly suggesting that a second primary cancer had developed. The remaining 3 tumor pairs demonstrated identical allelotypes consistent with regrowth of dormant tumor cells. CONCLUSION: Our results are consistent with the "field cancerization" hypothesis of ovarian carcinogenesis but could also be explained by a polyclonal tumor origin, which contrasts with the currently accepted monoclonal theory of ovarian carcinogenesis. Late development of a new primary cancer may herald the proband as a member of a familial cancer phenotype. These studies provide a molecular genetic rationale that both explains and prognosticates the clinical course of recurrent ovarian cancer.

Aged↗

Generation of a syngeneic mouse model to study the effects of vascular endothelial growth factor in ovarian carcinoma.

Vascular endothelial growth factor (VEGF) performs multifaceted functions in the tumor microenvironment promoting angiogenesis, suppressing anti-tumor immune response, and possibly exerting autocrine functions on tumor cells. However, appropriate syngeneic animal models for in vivo studies are lacking. Using retroviral transfection and fluorescence-activated cell sorting, we generated a C57BL6 murine ovarian carcinoma cell line that stably overexpresses the murine VEGF164 isoform and the enhanced green fluorescent protein. VEGF164 overexpression dramatically accelerated tumor growth and ascites formation, significantly enhanced tumor angiogenesis, and substantially promoted the survival of tumor cells in vivo. In vitro, VEGF164 overexpression significantly enhanced cell survival after growth factor withdrawal and conferred resistance to apoptosis induced by cis-platin through an autocrine mechanism. VEGF/green fluorescent protein-expressing tumors were not recognized by the adaptive immune system. After vaccination, a specific anti-tumor T-cell response was detected, but tumor growth was not inhibited. This engineered murine carcinoma model should prove useful in the investigation of the role of VEGF in modulating the tumor microenvironment and affecting the complex interactions among angiogenesis mechanisms, anti-tumor immune mechanisms, and tumor cell behavior at the natural state or during therapy in ovarian carcinoma.

Animals↗

CA 19-9 is an index of response to neoadjunctive chemoradiation therapy in pancreatic cancer.

PURPOSE: This study examines the changes of serum levels of CA 19-9 in patients with pancreatic cancer following neoadjuvant irradiation and chemotherapy to define the potential role of this tumor marker in preoperative management of these patients. MATERIALS AND METHODS: Serum CA 19-9 levels were measured in 42 patients before receiving external beam irradiation with concurrent 5-fluorouracil in preparation for laparotomy and Whipple procedure or intraoperative irradiation (IORT). The CA 19-9 levels were determined again after irradiation, and changes were correlated with findings of restaging computed tomography (CT) scan and laparotomy. RESULTS: Following preoperative irradiation, 10 patients (24%) experienced an increase in CA 19-9 levels whereas 29 patients (69%) showed a decrease in CA 19-9. There was no change in the CA 19-9 levels of 3 patients (7%) after treatment. Of the 10 patients with increased CA 19-9 levels after irradiation, 9 (90%) had developed distant metastases or local tumor progression as determined by restaging CT scan or at laparotomy. In contrast, only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation demonstrated metastases or local tumor progression on restaging CT scan or at laparotomy. The correlation of CA 19-9 increase or decrease with disease progression or control, respectively, was statistically significant (P = 0.009). CONCLUSIONS: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy. A rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9 connotes disease control in the majority of patients. In developing strategies for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19-9 appears most useful for the identification of patients who manifest progressive tumor growth and metastasis in spite of this treatment.

Adult↗

Macroscopic ovarian involvement in murine plasmacytoma.

In all ovaries of BALB/c/Se/Si mice carriers of plasmacytoma LPC/I, a plasmacellular proliferation was histologically observed. In 30% of the examined mice the proliferation had reached a macroscopical expression. This finding has not been previously observed.

Animals↗

Rectosigmoid obstruction caused by ovarian cancer.

Out of a total of 379 patients with ovarian carcinoma a rectosigmoid stenosis was detected in 44 (12%). A barium enema was available in 27 cases, which revealed a severe stenosis (less than 1/2 lumen open) in 23, with an average length of 17 cm (5-40 cm). Five characteristic types of stenosis were found: solitary stenosis (n = 6), large spherical impression (n = 6), multiple stenoses (n = 4), long narrow tract (n = 6) and a total obstruction (n = 5). Desmoplastic reaction with tethering and/or parallel folds (n = 16) or fixation and/or angulation (n = 18) were frequently found, but tumour invasion was rare (n = 3). A sigmoid resection (n = 1) or colostomy (n = 3) was seldom needed, due to beneficial response to combined therapy.

Adult↗