Search PubMed⌕ Search

Biomedical subjects

Nobuo Yaegashi

Publications and source records attributed to Nobuo Yaegashi.

At least 37 records · Page 2Linked to original sources

A trial to restore defective human sperm centrosomal function.

BACKGROUND: In human fertilization, sperm centrosome function is essential for male and female pronuclear movement and fusion. In this study, we investigated the possibility of restoring human sperm centrosomal function in sperm exhibiting abnormalities in microtubule organization. METHODS: Semen was obtained from both a fertile donor and a patient with dysplasia of the fibrous sheath (DFS). Following heterologous ICSI using human sperm, we examined microtubules and chromatin configuration in bovine oocytes. Sperm were treated with dithiothreitol (DTT) prior to ICSI, while the oocytes were treated with the cytoskeletal stabilizer paclitaxel after ICSI. RESULTS: The combination of DTT and paclitaxel treatment induced microtubule organization in dead sperm from the fertile donor following heterologous ICSI. This treatment, however, was not effective for DFS sperm. In addition, expression of centrin, a protein functioning within the sperm centrosome, was reduced in DFS sperm from that of the normal levels observed in fertile donor sperm. CONCLUSION: These results indicate that sperm centrosomal function could be induced by the treatment of sperm with DTT before ICSI and of oocytes with paclitaxel after ICSI. DFS sperm are likely to exhibit such severe dysfunction of sperm centrosome that cannot be compensated for by this treatment; therefore, this method may be a practical way to discern the degree of sperm centrosomal dysfunction.

Adult↗

Dynamic changes in the cytoskeleton during human spermiogenesis.

OBJECTIVE: To investigate the structural changes in the cytoskeleton (microtubules, microfilaments) and examine the expression of centrosomal functional proteins during human spermiogenesis. DESIGN: Immunofluorescent staining of human spermiogenic cells. SETTING: University hospital and IVF clinic. PATIENT(S): Human testicular tissues were obtained by testicular sperm aspiration (TESA) under informed consent. Three cases of obstructive azoospermia, with confirmed normal spermatogenesis, were examined. INTERVENTION(S): Spermatogenic cells were fixed with microtubule-stabilizing buffer. Immunocytochemical detection of microtubules, microfilaments, and centrosome was performed using monoclonal antibodies against alpha- and beta-tubulin, phalloidin, and functional centrosomal proteins. MAIN OUTCOME MEASURE(S): Samples were examined using epifluorescence and laser scanning confocal microscopes. RESULT(S): During the Sb2 period, microtubules formed the manchette structure, which extended from the equator of the nucleus through the cytoplasm. Microfilaments were organized in the periacrosamal region during spermiogenesis (Sa to Sd). Although centrin was observed throughout the spermiogenic period, gamma-tubulin was detected only in the Sb2 period. CONCLUSION(S): Dynamic cytoskeletal movement was observed during human spermiogenesis. Cytoskeletal rearrangements in the Sb2 period appear to play important roles in the morphologic changes that occur during human spermiogenesis. Studies of the cytoskeletal system during spermiogenesis may help identify some causes of male infertility (e.g., teratozoospermia, maturation arrest).

Adult↗

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a prognostic factor in human endometrial carcinoma.

OBJECTIVE: Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed in endometrial carcinoma. Our goal was to investigate if ATP7B is expressed in endometrial carcinoma and whether its expression correlates with prognosis. METHODS: We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 51 endometrial endometrioid adenocarcinomas. 27 of 51 patients were treated with cisplatin-based chemotherapy after surgery. RESULTS: Cytoplasmic staining of tumor cells was observed in 37.3% (19/51 cases) of the analyzed carcinomas and no staining was observed in adjacent non-neoplastic cells. ATP7B positivity in the degree of differentiation of G2 and G3 carcinoma was significantly higher than that of G1 carcinoma (P = 0.019). The patients with ATP7B-positive tumors had a worse prognosis than that with ATP7B-negative tumors in overall survival and disease-free survival, respectively (P < 0.01). CONCLUSIONS: These findings suggest that overexpression of ATP7B expression in endometrial carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. ATP7B expression could be considered as a prognostic factor in patients with endometrial carcinoma.

Adenocarcinoma↗

Epithelioid leiomyosarcoma of the uterine cervix: a case report and review of the literature.

BACKGROUND: Epithelioid leiomyosarcomas arising from the uterine cervix are extremely rare neoplasms, with only three cases reported in the English literature. CASE: A 53-year-old Japanese woman was admitted to our university hospital due to massive vaginal bleeding from a cervical tumor. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Histological findings, including immunohistochemical study using desmin, SMA, cytokeratin, S-100, HMB-45, vimentin, melan-A, and CD68, led to a diagnosis of epithelioid leiomyosarcoma of the uterine cervix. The patient underwent adjuvant chemotherapy and has been disease-free for over 20 months. CONCLUSION: Immunohistochemical studies may be needed to differentiate among the alternative diagnoses of malignant melanoma, metastatic carcinoma, and epithelioid sarcoma. Additional cases are needed to develop optimal management strategies and to predict prognosis.

Female↗

Orphan nuclear receptor DAX-1 in human endometrium and its disorders.

DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1) is a recently characterized member of the orphan nuclear receptor family. DAX-1 functions as a global negative regulator of steroid hormone production. It inhibits adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1) pathway-dependent P450arom expression in cultured human endometriotic stromal cells and acts as a corepressor for estrogen receptors (ER). In this study we first examined the localization of DAX-1 in 46 normal cycling endometria, 36 cases of endometrial hyperplasia and 103 cases of endometrial carcinoma by using immunohistochemistry to elucidate the possible involvement of DAX-1 and its correlation to the status of Ad4BP/SF-1, a universal transcription factor of steroidogenesis. We then evaluated DAX-1 mRNA expression, using quantitative reverse transcription-polymerase chain reaction for DAX-1 in 33 cases of endometrial carcinoma for further characterization. We subsequently correlated these findings with various clinicopathological parameters of the cases. Ad4BP/SF-1 immunoreactivity was not detected in any human endometria examined. A significant inverse correlation was detected between the status of DAX-1 immunoreactivity and histological grade (P = 0.0003) in endometrial carcinoma. The labeling index (LI) values of DAX-1 in normal endometrium during the secretory phase (P < 0.0001) and hyperplasia (P < 0.0001) were significantly higher than that of carcinoma. No significant correlations were detected between DAX-1 immunoreactivity and amounts of aromatase mRNA. There was a statistically significant positive correlation between DAX-1 and ERalpha (P = 0.006) and ERbeta LI (P < 0.001). These findings suggest that DAX-1 may inhibit the proliferation and progression of endometrial carcinoma through inhibition of estrogenic actions, possibly by interacting with ER present in carcinoma cells, rather than regulating in situ steroidogenesis.

Adrenal Glands↗

Successful conservative treatment of a cesarean scar pregnancy with uterine artery embolization.

Ectopic pregnancy developing in a previous Cesarean section scar is rare and is associated with catastrophic complications, such as uterine rupture and uncontrollable bleeding, which may lead to loss of the uterus. The operative treatments that have been reported for cesarean scar pregnancy are dilatation and curettage and excision of trophoblastic tissues using either laparotomy or laparoscopy. Recently, conservative treatment of scar pregnancy with locally and/or systemically administered methotrexate (MTX) has been reported. However, recent reports demonstrated that cases treated with MTX sometimes required laparotomy later because of excessive bleeding. In this series of cases we have demonstrated that viable cesarean scar pregnancies can be treated safely by selective transarterial embolization in combination with subsequent dilatation and curettage and local or systemic injections of MTX. In these three cases, uterine artery embolization proved to be a useful procedure for preventing uncontrollable bleeding and unnecessary uterine loss.

Abortion, Induced↗

Ber-EP4 and anti-calretinin antibodies: a useful combination for differential diagnosis of various histological types of ovarian cancer cells and mesothelial cells.

The differential diagnosis between reactive mesothelial cells and ovarian carcinoma cells is often difficult in cytologic specimens. Immunocytochemical procedures have been utilized in assisting this differential diagnosis, with limitations. Furthermore, previous studies examined only serous type but not other histological types of ovarian carcinoma cases. Therefore, we evaluated the practical value of various epithelial and mesothelial markers in differential diagnosis of these two types of cells. Various types of ovarian carcinoma (serous, n = 22; mucinous, n = 10; endometrioid, n = 7; clear cell, n = 10) and benign mesothelial tissues (n = 15) were studied by immunohistochemistry. We then studied effective panels of antibodies by immunohistochemistry in 43 cytologic specimens of ascites or peritoneal lavage fluid consisting of 20 reactive mesothelium and 23 adenocarcinomas of the ovary. In the tissue specimens, Ber-EP4, a monoclonal antibody of epithelial antigen, and a polyclonal antibody against calretinin, which is expressed in mesothelium, are used in differentiating reactive mesothelial cells from ovarian carcinoma. In cytologic specimens, the sensitivity and specificity of Ber-EP4 were 100% and 90%, respectively. The sensitivity and specificity of the anti-calretinin antibody were 90% and 91%, respectively. Using multiple regression analysis, the correlation coefficient between epithelial antigen and calretinin reactivity was r = 0.938, with a significance level of p < 0.0001. In conclusion, the combined immunostaining of cytologic specimens for Ber-EP4 and the anti-calretinin antibody is helpful for the differential diagnosis between mesothelial cells and not only serous type, but also mucinous, endometrioid and clear cell types of ovarian cancer cells.

Antibodies↗

Genetic significance of skewed X-chromosome inactivation in premature ovarian failure.

To determine the relationship between premature ovarian failure (POF) and skewed X-chromosome inactivation (XCI), karyotype, and XCI status in 43 patients with POF (group I) and 43 age-matched control women with regular menstrual cycles (group II) were evaluated. Evaluation of XCI status was based on the CAG triplet repeat polymorphism assay in the androgen receptor gene after sodium bisulfite treatment of DNA samples, and XCI patterns were classified as random (XCI < 70% skewing) or skewed (> or =70%). Furthermore, skewed XCI was classified under three different thresholds (> or =70, > or =80, or > or =90%). Karyotyping by G-banding and fluorescence in situ hybridization (FISH) on peripheral blood lymphocytes showed that one patient in group I had a deletion of Xq22, and another was 47,XXX. The frequency of low-level 45,X/46,XX mosaicism was nearly equal in both groups. In women without any X-chromosomal aberrations, the incidence of skewed XCI in group I was significantly higher than in group II on all threshold levels. Furthermore, extremely skewed XCI (> or =90%) was observed only in group I. These results indicate that POF may be caused by some underlying genetic disorders, which may induce skewed XCI.

Adult↗

Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma.

PURPOSE: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined. EXPERIMENTAL DESIGN: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17beta-hydroxysteroid dehydrogenase type 1 and type 2. RESULTS: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients. CONCLUSIONS: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.

17-Hydroxysteroid Dehydrogenases↗

Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy.

PURPOSE: A major obstacle in the treatment of ovarian carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Cu-transporting ATPase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate ATP7B expression in ovarian carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment. EXPERIMENTAL DESIGN: We retrospectively examined the expression of ATP7B and p53 in primary ovarian carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 104 ovarian carcinomas patients who received cisplatin-based chemotherapy. We performed immunohistochemical analysis of ATP7B and p53 using a monoclonal antibody against ATP7B and DO7 antibody against p53 protein in 104 ovarian carcinomas and adjacent nonneoplastic tissues. The significance of ATP7B and p53 in the prognosis of patients with ovarian carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1988 and 2001. Furthermore, mutation analysis at the six Cu-binding domain and ATP-binding domain, which may be important for cisplatin transport, were performed using single-strand conformational polymorphism after reverse transcriptase-PCR. RESULTS: A variable degree of cytoplasmic staining of ATP7B in tumor cells was observed in 34.6% (36 of 104 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent nonneoplastic tissues. ATP7B positivity in poorly/moderately differentiated carcinoma was significantly higher than that in low malignant potential tumor/well-differentiated carcinoma (P = 0.0276). Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P = 0.025). The multivariate Cox regression analysis revealed that ATP7B expression (hazard ratio, 1.8; 95% confidence interval, 1.0-3.2, P = 0.048), as well as International Federation of Gynecologists and Obstetricians stage (hazard ratio, 2.0; 95% confidence interval, 1.1-3.6, P = 0.018), was prognostic for poor disease outcome after adjustment for p53 expression, grade, and residual tumor. p53 expression was detected in 31.5% (26/104 cases). No mutation was observed on the six Cu-binding domain or ATP-binding domain in human ovarian carcinomas expressing ATP7B gene. CONCLUSIONS: This study demonstrates that overexpression of ATP7B in ovarian carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B expression may be considered as a predictive marker of chemoresistance for cisplatin-based chemotherapy in patients with ovarian carcinoma. We further predict that drugs targeting ATP7B might be useful in combination with cisplatin-based regimen for the improvement of patients with ovarian carcinoma.

Adenosine Triphosphatases↗

Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation.

PURPOSE: In this study, we examined the promoter methylation status and expression of 14-3-3 sigma and evaluated its clinical significance in epithelial ovarian cancer. EXPERIMENTAL DESIGN: Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3 sigma gene and protein. RESULTS: Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P < 0.001). Treatment of 5-aza-2'-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3 sigma protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3 sigma protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3 sigma was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of >2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3 sigma immunoreactivity was significantly associated with overall survival (P = 0.0058). CONCLUSIONS: Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.

14-3-3 Proteins↗

Centrosomal function assessment in human sperm using heterologous ICSI with rabbit eggs: a new male factor infertility assay.

Sperm centrosomal function was assessed by immunocytochemical analysis after the injection of human sperm into mature rabbit eggs. Three hours after intracytoplasmic sperm injection (ICSI), an astral microtubule array from the base of the human sperm was observed in the rabbit eggs. This sperm aster expanded in the egg cytoplasm, concomitant with pronuclear formation, and a dense microtubule array was organized at the time of pronuclear centration. Using fertile donor sperm, the sperm aster formation rate at 3 hr after ICSI was 35.0 +/- 1.5%. Using sperm from infertile patients, the average aster formation rate was lower (25.4 +/- 14.8%, P<0.05). Among infertile cases, there was no correlation between sperm aster formation rates and conventional parameters of semen analysis. However, the sperm aster formation rate correlated with the embryonic cleavage rate following human in vitro fertilization (IVF). These data suggest that this assay reflects sperm function during embryonic development after sperm entry and that reproductive success during the first cell cycle requires a functional sperm centrosome. Furthermore, sperm centrosomal function cannot be predicted from conventional parameters of semen analysis. We propose that insufficient centrosomal function could be the cause of certain cases of idiopathic infertility. These assays may lead to the discovery of new types of infertility, which have previously been treated as "unexplained infertility," and may also lead to the treatment of infertility incurable even by ICSI. Consequently, an accurate and relevant assay to help assure couples of the success of fertilization is warranted, perhaps prior to ICSI therapy.

Animals↗

Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma.

BACKGROUND: Interleukin-18 (IL-18), a cytokine produced by macrophages, is capable of inducing T-lymphocyte synthesis of interferon-gamma (IFN-gamma). In this study, for the first time, the serum concentration of IL-18 and its significance as a prognostic indicator was evaluated in patients with epithelial ovarian cancer. METHODS: The serum IL-18 level was measured by an enzyme-linked immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8 healthy controls. Relationships between the IL-18 level and clinicopathological features were examined by univariate and multivariate analyses. RESULTS: The median serum IL-18 level in the ovarian cancer patients was 229.6 pg/ml, and the level was significantly elevated compared with that in the normal controls (151.3 pg/ml; P < 0.01). No significant correlations were detected between the IL-18 level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate analysis, overall survival was shown to be affected by IL-18 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-18 serum levels, while confirming the role of previously established prognostic variables, such as performance status, stage, and residual tumor. CONCLUSION: This study showed that IL-18 serum levels were elevated in ovarian cancer patients and were correlated with overall survival, although they were shown not to be an independent prognostic factor.

Adult↗

A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina.

We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms.

Aged↗

Sentinel lymph node detection in patients with endometrial cancer.

OBJECTIVE: The purpose of this study was to examine the feasibility of sentinel lymph node (SLN) detection in patients with endometrial cancer using preoperative lymphoscintigraphy and an intraoperative gamma probe. PATIENTS AND METHODS: Between June 2001 and January 2003, 28 consecutive patients with endometrial cancer who were scheduled for total abdominal hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy, and paraaortic lymphadenectomy at Tohoku University School of Medicine underwent sentinel lymph node detection. On the day before surgery, preoperative lymphoscintigraphy was performed by injection of 99m-Technetium ((99m)Tc)-labeled phytate into the endometrium during hysteroscopy. At the time of surgery, a gamma-detecting probe was used to locate radioactive lymph nodes. RESULTS: At least one sentinel node was detected in each of 23 of the 28 patients (82%). The mean number of sentinel nodes detected was 3.1 (range, 1-9). Sentinel nodes could be identified in 21 of 22 patients (95%) whose tumor did not invade more than halfway into the myometrium. Eighteen patients had radioactive nodes in the paraaortic area. Most patients had a sentinel node in one of the following three sites: paraaortic, external iliac, and obturator. The sensitivity and specificity for detecting lymph node metastases were both 100%. CONCLUSION: The combination of preoperative lymphoscintigraphy with intraoperative gamma probe detection may be useful in identifying sentinel nodes in early-stage endometrial cancer.

Adult↗

Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.

OBJECTIVE: The purpose of this study was to examine sentinel lymph node (SLN) detection in patients with early stage cervical cancer using (99m)Tc phytate and patent blue dye and to compare our method with published findings utilizing other radioisotopic tracers. PATIENTS AND METHODS: A total of 20 consecutive patients with cervical cancer scheduled for radical hysterectomy and total pelvic lymphadenectomy at our hospital underwent SLN detection study. The day before surgery, lymphoscintigraphy was performed with injection of 99m-technetium ((99m)Tc)-labeled phytate into the uterine cervix. At surgery, patients underwent lymphatic mapping with a gamma-detecting probe and patent blue injected into the same points as the phytate solution. RESULTS: At least one positive node was detected in 18 patients (90%). A total of 46 sentinel nodes were detected (mean, 2.3; range, 1-5). Most sentinel nodes were in one of the following sites: external iliac (21 nodes), obturator (15 nodes), and parametrial (7 nodes). Eleven (24%) sentinel nodes were detected only through radioactivity and two (4%) were detected only with blue dye. The sensitivity, specificity, and negative predictive value for SLN detection were all 100%. Nine published studies involving 295 patients had a summarized detection rate of 85%. Summarized sensitivity, specificity, and negative predictive value were 93%, 100%, and 99%, respectively. CONCLUSION: Combination of (99m)Tc phytate and patent blue is effective in SLN detection in early stage cervical cancer.

Adult↗

Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of combination chemotherapy with paclitaxel and carboplatin in patients with advanced or recurrent carcinosarcoma of the uterus. METHODS: A retrospective review was carried out at Miyagi Prefecture Cancer Research Center Hospital. Six patients pathologically diagnosed with uterine carcinosarcoma were treated with paclitaxel (175 mg/m(2) given intravenously over 3 h) and carboplatin (dosed at AUC 6) every 3 weeks at our center between 1997 and 2003. Responses and adverse effects were assessed according to Response Evaluation Criteria in Solid Tumors and National Cancer Institute-Common Toxic Criteria, respectively. RESULTS: All six patients were evaluable for toxicity, and no unacceptably severe toxicities were reported. Grades 3 and 4 hematologic toxicities occurred, but all of them were overcome by adequate treatment with granulocyte colony-stimulating factor and blood transfusions. Five of six patients had measurable disease and thus were evaluable for response: Four patients had a complete response (CR) and the remaining patient had progressive disease (PD). The median progression-free interval (PFI) for all six cases was 18 months, with a median overall survival of 25 months. CONCLUSIONS: Although the number of cases was small, the regimen evaluated in the current study demonstrated higher activity and lesser toxicity than those found in previous studies in patients with advanced or recurrent uterine carcinosarcoma. Additional phase II clinical studies are necessary to evaluate fully the benefits of this regimen.

Antineoplastic Combined Chemotherapy Protocols↗

Primary vaginal adenosarcoma with sarcomatous overgrowth.

BACKGROUND: Primary vaginal adenosarcomas are extremely rare, and typical adenosarcomas are of low malignancy. However, aggressive forms with sarcomatous overgrowth have been reported, those appear to have a poor prognosis. CASE: A 52-year-old woman who had undergone prior surgery for uterine leiomyoma and an ovarian cyst (total abdominal hysterectomy and left salpingo-oophorectomy) presented 10 years later with a rapidly enlarging tumor arising from the vaginal cuff. Repetitive biopsy samples revealed a mixture of benign epithelial gland and malignant stromal components with periglandular stromal hypercellularity and sarcomatous overgrowth. A histological diagnosis of mullerian adenocarcinoma was made. The patient died from recurrent disease 9 months after surgery. CONCLUSION: Regardless of primary focus, adenosarcoma with sarcomatous overgrowth is associated with postoperative recurrence and a fatal outcome.

Adenosarcoma↗