A phase II study of combination chemotherapy using docetaxel and irinotecan for TC-refractory or TC-resistant ovarian carcinomas (GOGO-OV2 study) and for primary clear or mucinous ovarian carcinomas (GOGO-OV3 Study).

OBJECTIVE: To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas. STUDY DESIGN: Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study. RESULTS: A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable. CONCLUSION: Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.

Grave outcome of granulocyte colony-stimulating factor-producing endometrial cancer: a case report and literature review.

Granulocyte colony-stimulating factor (G-CSF)-producing nonhematopoietic malignancies have been reported in various organs, and most of them have been associated with poor clinical outcome. However, because of the rarity of reported cases, information regarding G-CSF-producing gynecological malignancies, especially uterine corpus cancer, is limited. We report a case of G-CSF-producing endometrial cancer, which exhibited a grave clinical outcome. Our case strongly indicates the aggressive nature of G-CSF-producing endometrial cancer.

Targeting SRC in mucinous ovarian carcinoma.

PURPOSE: Mucinous ovarian carcinomas have a distinct clinical pattern compared with other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of Src kinase in preclinical models of mucinous ovarian carcinoma. EXPERIMENTAL DESIGN: A total of 1,302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of Src kinase inhibition were tested using dasatinib-based therapy in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2). RESULTS: Patients with advanced-stage mucinous ovarian cancer had significantly worse survival than those with serous histology: median overall survival, 1.67 versus 3.41 years, P = 0.002; median survival time after recurrence of 0.53 versus 1.66 years, P < 0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest Src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of Src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting Src with dasatinib in vivo showed significant antitumor effects in the RMUG-S-ip2 model but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further showed significant effects on reducing cell viability, increasing apoptosis, and in vivo antitumor effects in the RMUG-S-ip2 model. CONCLUSIONS: Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting Src kinase with a combination of dasatinib and oxaliplatin may be an attractive approach for this disease.

Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy.

BACKGROUND: TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined. PATIENTS AND METHODS: Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed. RESULTS: The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy. CONCLUSION: TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

Recurrent endometrial carcinoma: prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later.

OBJECTIVE: We evaluated association of prognosis of endometrial carcinoma patients and treatment-free intervals (TFIs). STUDY DESIGN: We compared the effectiveness of second-line chemotherapy performed for patients with TFIs of 6-12 months and 12 or more months following a first-line chemotherapy based on taxane (paclitaxel) and carboplatin, with or without the anthracycline (TC). RESULTS: Progression-free and overall survivals were significantly shorter in patients with TFIs of 6-12 months than those with TFIs of 12 or more months. Among the patients who received similar second-line chemotherapy, response rates of 15 patients with TFIs of 12 or more months and 7 patients with TFIs of 6-12 months were 67% and 43%, respectively. Progression-free survival was significantly worse in those with TFIs of 6-12 months (median, 7 months) than those with TFIs of 12 or more months (median, 12 months). CONCLUSION: Our small retrospective analysis suggests that recurrent endometrial carcinomas with TFIs of 6-12 months can be regarded as being partially sensitive to TC-based chemotherapy.

Disease-free interval after primary treatment predicts prognosis of recurrent endometrial carcinoma.

AIM: The aim of this study was to determine if the disease-free interval after initial surgical resection has any useful prognostic value for recurrent endometrial carcinoma patients. PATIENTS AND METHODS: Between 1998 and 2007, complete resection of endometrial carcinoma was achieved in 536 cases at the Departments of Obstetrics and Gynecology of the Osaka University and Osaka Rosai Hospitals of Osaka, Japan. Clinical characteristics of these cases were retrospectively reviewed. RESULTS: Recurrence was subsequently detected in 54 cases. Overall survival after recurrence in 27 patients with recurrences earlier than 12 months who received no postoperative therapy, radiation, and chemotherapy as an adjuvant therapy were significantly shorter than that of those with recurrences later than 12 months with similar treatments. Multivariate analysis demonstrated that the disease-free interval was an independent factor for prognosis. CONCLUSION: We demonstrate a significantly worse prognosis in cases with early versus late recurrence of resected endometrial carcinomas, irrespective of the type of adjuvant therapy.

Amputation of uterine corpus as the intraoperative modification during cesarean radical hysterectomy for invasive cervical cancer during pregnancy.

OBJECTIVE: Cesarean radical hysterectomy (CRH) for invasive cervical cancer during pregnancy is characterized by heavy blood loss. Any surgical modifications made in an attempt to reduce the blood loss are valuable. Our study was designed to evaluate the efficacy of amputating the uterine corpus during CRH. METHODS: All cases of radical hysterectomy (RH) were evaluated. Cases were divided into: (a) cesarean section immediately followed by RH for invasive cervical cancer complicating pregnancy (CRH group); and (b) RH for nonpregnant subjects (RH group). The information abstracted included estimated blood loss (EBL), operative time, intraoperative transfusion, and use of amputation of uterine corpus during CRH. Nonparametric tests were used for the statistical analysis. RESULTS: There were five CRH cases (3 for CRH with amputation, 2 for CRH without amputation) and 209 RH cases were evaluated for statistics during the study period. The difference in mean operative time between the CRH group and the RH group was not statistically significant: 276.6 min (range 160-425) versus 297.3 min (range 147-645), p = 0.66. The mean EBL for the CRH group was significantly larger than that for the RH group: 2106.6 ml (range 730-4150) versus 858.8 ml (range 150-4770), p < 0.001. Mean operative time and mean EBL for CRH with amputation of uterine corpus were significantly less than those for CRH without amputation of uterine corpus: operative time, 186.0 min (range 160-228) versus 412.5 min (range 400-425), p = 0.043; EBL, 1034.3 ml (range 730-1540) versus 3715.0 ml (range 3280-4150), p = 0.043. No intraoperative tumor exposures were observed in the amputated cases. CONCLUSION: Amputation of uterine corpus during CRH for invasive cervical cancer during pregnancy significantly improves the intraoperative performance, although it should be used with care.

Postoperative abdominal aspergilloma mimicking cervical cancer recurrence and diagnostic imaging, including F-fluorodeoxyglucose positron emission tomography, with false-positive findings.

We present the case of a 39-year-old woman with a subfascial abscess. The patient had undergone radical hysterectomy for stage Ib1 cervical cancer. Six months after the surgery, she was found to have an elevated concentration of the serum squamous cell carcinoma antigen. Thereafter, she underwent magnetic resonance imaging and positron emission tomography-computed tomography. Magnetic resonance imaging revealed an irregular mass (diameter: 2 cm) in the abdominal wall. Increased (18)F-fluorodeoxyglucose uptake into the mass was observed on positron emission tomography. Therefore, we could not rule out the possibility of the peritoneal dissemination of cervical cancer, and we resected the mass. The mass was pathologically and microbiologically diagnosed as a subfascial aspergilloma. The lesion was located in the subfascial area where a drain was inserted at the time of the primary laparotomy.

A novel technique for the management of the vesicouterine ligament during radical hysterectomy.

OBJECTIVE: To introduce a simple and safe method for the management of the vesicouterine ligament (VUL) during radical hysterectomy. METHOD: From 2004 to 2006, 35 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 (n=32) and IB2 (n=3) invasive cervical cancer underwent radical hysterectomy. Epinephrine, which was diluted 1:1,000,000 times with saline solution, was injected into the VUL. We investigated whether this hydrodissection technique is safe and simple to apply in the management of the VUL during radical hysterectomy. RESULT: The hydrodissection technique enabled us to easily identify cervicovesical vessels. As a result, none of the patients suffered ureteral injury during radical hysterectomy. CONCLUSION: The injection of diluted epinephrine into the VUL is safe and simple to apply in the management of the VUL during radical hysterectomy.

Use of uterine fundal pressure maneuver at vaginal delivery and risk of severe perineal laceration.

OBJECTIVE: Owing to the lack of evidence supporting the use of uterine fundal pressure maneuver in vaginal delivery, the role of the maneuver is undetermined and remains controversial. The aim of this study was to identify the prone factor of the use of uterine fundal pressure maneuver and to evaluate its obstetrical outcomes. METHODS: All vaginal delivery records between 1 January 2005 and 30 April 2006 were evaluated. Maternal and neonatal variables and obstetrical complications were analyzed for subjects underwent uterine fundal pressure maneuver. RESULTS: Six hundred sixty-one vaginal deliveries were evaluated. Fundal pressure maneuver was performed in 39 cases (5.9%, 95% CI 4.4-7.1). Primiparity (76.9 vs. 53.3%; odds ratio 2.92, 95% CI 1.36-6.25, P = 0.004), larger maternal body weight gain during pregnancy (11.16 +/- 0.4 kg vs. 10.05 +/- 0.16 kg, P = 0.013), and longer duration of labor (922.3 +/- 111.7 vs. 566.6 +/- 18.3 min, P = 0.003) were prone risk factors for the use of uterine fundal pressure maneuver at vaginal delivery. One case of shoulder dystocia following uterine fundal pressure maneuver was reported (2.5 vs. 0%). Episiotomy (76.9 vs. 44.9%, P < 0.001) and vacuum extraction (41.0 vs. 3.8%, P < 0.001) were frequently performed with uterine fundal pressure maneuver. Uterine fundal pressure maneuver increased the risk of severe perineal laceration (28.1 vs. 4.8%; odds ratio 2.71, 95% CI 1.03-7.15, P = 0.045). The risk of severe perineal laceration was synergistically increased with the concurrent use of uterine fundal pressure maneuver with vacuum extraction and episiotomy. CONCLUSION: Uterine fundal pressure maneuver during the second stage of labor increased the risk of severe perineal laceration. The use of the maneuver must be cautioned and careful attention must be paid to its application.

Detection of the draining vein from hepatic focal nodular hyperplasia on three-dimensional computed tomography.

It is sometimes difficult to differentiate focal nodular hyperplasia from other hepatic tumors. A report is presented of a patient in whom three-dimensional computed tomography was useful to diagnose focal nodular hyperplasia of the liver. In a 31-year-old women with epigastralgia, ultrasonography and computed tomograms showed a tumor in the liver. Three-dimensional computed tomograms showed a hypervascular lesion with a hypodense interior and feeding arteries on early images. On delayed images, a draining vein connecting with the hepatic vein was clearly demonstrated. Although focal nodular hyperplasia was strongly suspected, the tumor was resected because of the enlargement and extrahepatic growth of the tumor. Pathologic examination showed that the tumor was focal nodular hyperplasia of the liver. A draining vein connecting to the hepatic vein may be a characteristic of focal nodular hyperplasia. Three-dimensional computed tomography may be useful to diagnose focal nodular hyperplasia of the liver.

Uterine rupture of cesarean scar related to spontaneous abortion in the first trimester.

We report the case of a 31-year-old Japanese female diagnosed by transvaginal ultrasonography to have a spontaneous uterine rupture in the first trimester. Her condition was complicated by diabetes mellitus type 1. Her previous pregnancy had resulted in an emergency cesarean section by transverse incision of the lower uterine segment with single-layer suture at 37(+4) weeks of gestation. Transvaginal ultrasonography displayed both a gestational sac located in the anterior lower uterine segment and a defect in the uterine wall located at the site of the previous cesarean delivery scar. Pelvic magnetic resonance imaging showed that the uterine muscle layer was discontinuous and the gestational sac was almost outside the uterine cavity, accompanied by mild hemorrhaging within the endometrial cavity. The defect in the lower uterine wall was round in shape and was 3 cm in diameter. Since uterine ruptures can occur during all gestational periods, it is important to pay attention to the uterine wall where any cesarean incision was previously made.