Analysis of gastric-type mucinous carcinoma of the uterine cervix - An aggressive tumor with a poor prognosis: A multi-institutional study.

OBJECTIVE: Gastric-type mucinous carcinoma (GAS) is a novel variant of mucinous carcinoma of the uterine cervix. As shown in the original Japanese group description, in recent studies, GAS represents a more aggressive disease than the usual-type endocervical adenocarcinoma (UEA). Detailed clinicopathological features of this variant remain to be elucidated in a larger series of patients. METHODS: Patients were enrolled by the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group after receiving the approval of each Institutional Review Board. The study population comprised of women with stage I to II endocervical adenocarcinomas who underwent surgery between 2000 and 2009. Representative slides were evaluated by central pathological review (CPR), categorized into either GAS or UEA, and correlated with clinicopathological features and outcome. RESULTS: Among the 393 enrolled patients with endocervical adenocarcinoma, 328 patients met the criteria for CPR and the study eligibility criteria and were included in further analysis. A total of 95 of the 328 tumors were classified as GAS. Compared with UEA, GAS was more significantly associated with bulky mass, deep stromal invasion, lymphovascular space invasion, parametrial invasion, ovarian metastasis, positive ascitic fluid cytology, pelvic lymph node metastasis, and pathological (p) T stage but was not related to the degree of histological differentiation. Disease-free survival (P < 0.0001) and overall survival (P < 0.0001) were poorer in patients with GAS than in those with UEA. CONCLUSIONS: GAS showed aggressive behavior with ominous histopathological predictors as well as decreased survival. GAS is therefore considered a distinct entity that should be distinguished from UEA. CLINICAL TRIAL INFORMATION: UMIN Clinical Trials Registry: UMIN000007987.

Phase III study of cisplatin with or without S-1 in patients with stage IVB, recurrent, or persistent cervical cancer.

BACKGROUND: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer. METHODS: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m2 was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS). RESULTS: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs. CONCLUSIONS: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population.

Breakthrough chemotherapy-induced nausea and vomiting: report of a nationwide survey by the CINV Study Group of Japan.

BACKGROUND: We conducted a nationwide survey on chemotherapy-induced nausea and vomiting (CINV) in Japan and demonstrated good compliance with Japanese CINV guidelines, resulting in good control of vomiting. However, almost half the patients experienced breakthrough CINV. We analyzed the survey results in relationship to the management of patients with breakthrough CINV. METHODS: This multicenter, prospective, observational study analyzed data for 1910 patients in Japan scheduled for moderately or highly emetogenic chemotherapy (MEC and HEC, respectively). Patients who developed CINV despite prophylactic use of antiemetics were administered rescue drugs. Patients who received cisplatin-based HEC (C-HEC), non-cisplatin-based HEC (N-HEC), or MEC were evaluated separately. RESULTS: A total of 989 patients experienced CINV, of whom 412 (44%) received rescue antiemetics during the study period. The rate at which patients with breakthrough CINV were started on rescue drugs ranged from 13% to 24%. Rescue drugs were given more frequently on days 2-4 for C-HEC and MEC and on days 1-2 for N-HEC. Eighty-six percent of patients received metoclopramide or domperidone. 5-HT3 receptor antagonists, antipsychotics, and anti-anxiety drugs were used for 11-5% of patients. The mean duration of antiemetic use was 2.6 days. CONCLUSIONS: Fewer than half of the patients with breakthrough CINV were treated with rescue antiemetics, suggesting that CINV was mild in the remaining patients. However, CINV was sufficiently severe to prevent eating in other patients, indicating the need for new drugs with different mechanisms to control CINV.

A prospective observational study on chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer by the CINV Study Group of Japan.

OBJECTIVE: This study was performed to investigate the occurrence of and risk factors for chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer. METHODS: In total, 214 patients with gynecologic cancer who underwent highly emetogenic (HEC) or moderately emetogenic chemotherapy (MEC) were evaluated. We investigated the relationship between CINV and clinical factors and the accuracy of estimation of CINV by medical staff in the acute and late phases. Vomiting was evaluated in terms of frequency, and nausea was evaluated with a 100-mm visual analog scale on days 1 to 7. We also analyzed the risk factors and changes in CINV over time using a generalized linear mixed (GLM) model. RESULTS: The multivariate analysis revealed no significant risk factors for acute CINV. The independent risk factors for delayed nausea were a morning sickness history (odds ratio [OR], 2.687; 95% confidence interval [95% CI], 1.450-4.976; p=0.0017), age (each 1-year increment) (OR, 0.97; 95% CI, 0.944-0.996; p=0.0235), and HEC (OR, 2.134; 95% CI, 1.039-4.383; p=0.0391). The GLM model demonstrated that the independent factors affecting nausea were significant morning sickness (p=0.0101) and HEC (p=0.0136). These data also showed more severe nausea from days 3 to 5, but the negative predictive value for estimation of delayed nausea by medical staff was 57.8%. CONCLUSION: Our data suggest that improvement of preventive antiemetic administration is needed for patients with risk factors to manage delayed CINV caused by HEC and by MEC.

Personalized peptide vaccination for cervical cancer patients who have received prior platinum-based chemotherapy.

A feasibility study was performed to evaluate the immunological efficacy and safety of a personalized peptide vaccine (PPV) for cervical cancer patients who have received platinum-based chemotherapy. A total of 24 patients with standard chemotherapy-resistant cervical cancer, including 18 recurrent cases, were enrolled in this study and received a maximum of 4 peptides based on HLA-A types and IgG levels to the vaccine candidate peptides in pre-vaccination plasma. The parental protein expression of most of the vaccine peptides was confirmed in the cervical cancer tissues. No vaccine-related systemic grade 3 or 4 adverse events were observed in any patients. Due to disease progression, 2 patients failed to complete the first cycle of vaccinations (sixth vaccination). Cytotoxic T-lymphocyte (CTL) or IgG responses specific for the peptides used for vaccination were augmented in half of cases after the first cycle. The median overall survival was 8.3 months. The clinical responses of the evaluable 18 cases consisted of 1 case with a partial response and 17 cases with disease progression; the remaining 6 cases were not evaluable. Performance status, injection site skin reaction and circulating PD-1(+) CD4(+) T-cells were significantly prognostic of overall survival, and multivariate analysis also indicated that the performance status and circulating PD-1(+) CD4(+) T-cells were prognostic. Because of the safety and immunological efficacy of PPV and the possible prolongation of overall survival, further clinical trials of PPV at a larger scale in advanced or recurrent cervical cancer patients who have received prior platinum-based chemotherapy are recommended.

Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).

OBJECTIVE: To assess the safety and efficacy of the combination of oral etoposide and intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer. METHODS: Eligible patients (age, 20-75years; platinum-free interval, ≤28weeks) with an adequate organ function received oral etoposide (50mg/m(2) once a day) from day 1 to day 21 and intravenous irinotecan (70mg/m(2)) on days 1 and 15. The regimen was repeated every 28days up to 6cycles. The primary endpoint was the response rate (RR) with a threshold of 20%. The response was evaluated according to RECIST 1.0 and Gynecologic Cancer Intergroup CA-125 Response Definition, and toxicities were evaluated according to CTCAE version 3.0. This trial was registered at UMIN-CTR as UMIN000001837. RESULTS: Between April 1, 2009 and January 20, 2012, 61 patients were enrolled. Sixty patients were eligible. 1 CR and 12 PRs were confirmed; RR was 21.7% (p=0.42, the exact binomial test). PFS and OS were 4.1 and 11.9months, respectively. Major toxicities of ≥grade 3 were neutropenia (60%), anemia (36.7%), thrombocytopenia (11.7%), febrile neutropenia (18.3%), fatigue (13.3%), anorexia (11.7%), and nausea (11.7%). Three patients died from treatment related death (interstitial pneumonia, a pulmonary embolism, and DIC due to infection). Two of these patients were aged ≥65years. CONCLUSIONS: Oral etoposide and intravenous irinotecan had a moderate RR but did not meet the primary endpoint. Because of toxicity, we do not recommend this regimen outside of clinical trials. In particular, when considering this regimen for elderly patients, extreme caution is advised.

Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A).

OBJECTIVE: In order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter≤2 cm were investigated. METHODS: We conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2 cm or less (cT≤2 cm) and ii) greater than 2 cm (cT>2 cm). We expected 5-year OS of ≥95% and parametrial involvement<2-3% for patients with cT≤2 cm who underwent radical hysterectomy. RESULTS: Of the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2 cm and 248 with cT>2 cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2 cm and 12.9% (32/248) with cT>2 cm. Five-year overall survivals were 95.8% (95% CI 92.9-97.6%) in cT≤2 cm and 91.9% (95% CI 87.6-94.8%) in cT>2 cm patients. CONCLUSION: Patients with cT≤2 cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery.

Non-randomized confirmatory trial of modified radical hysterectomy for patients with tumor diameter 2 cm or less FIGO Stage IB1 uterine cervical cancer: Japan Clinical Oncology Group Study (JCOG1101).

A non-randomized confirmatory trial was started in Japan to evaluate the efficacy of modified radical hysterectomy in patients with tumor diameter 2 cm or less FIGO Stage IB1 uterine cervical cancer, for which the current standard is radical hysterectomy. This study began in January 2013 and a total of 240 patients will be accrued from 37 institutions within 3 years. The primary endpoint is 5-year survival. The secondary endpoints are overall survival, relapse-free survival, local relapse-free survival, percent completion of modified radical hysterectomy, percent local relapse, percent pathological parametrial involvement, days until self-urination and residual urine disappearance, blood loss, operation time, percent post-operative radiation therapy, adverse events and severe adverse events. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000009726 (http://www.umin.ac.jp/ctr/).

Testing the effectiveness of antiemetic guidelines: results of a prospective registry by the CINV Study Group of Japan.

BACKGROUND: Many cancer patients suffer from the common side effect of chemotherapy-induced nausea and vomiting (CINV). Guidelines recommend a combination of two prophylactic antiemetics for moderately emetogenic chemotherapy (MEC) and three for highly emetogenic chemotherapy (HEC) and certain MEC regimens. METHODS: This multicenter, prospective, observational study analyzed data for 1,910 patients in Japan scheduled for MEC or HEC. Use of antiemetic prophylaxis in relation to type of chemotherapy, incidences of and risk factors for nausea, vomiting, and acute versus delayed CINV, and estimated incidence of CINV by staff were analyzed using Fisher's exact test and multivariate logistic regression. The patients recorded the incidence of CINV and severity of nausea by visual analogue scales daily for 7 days after receiving chemotherapy. RESULTS: A total of 240 (20.1 %) HEC and 476 MEC patients (66.6 %) received 2 antiemetics, compared with 883 (73.9 %) and 200 (28.0 %), respectively, who received 3 antiemetics. Approximately 74 % of HEC and 95 % of MEC patients received antiemetic therapy in compliance with guidelines. Acute nausea and vomiting were well controlled, but high incidences of delayed nausea occurred in both HEC and MEC patients. Delayed vomiting (p < 0.0001) was significantly less frequent in patients receiving three compared with 2 antiemetics. Female sex was a major risk factor for CINV. Medical staff tended to overestimate the incidence of CINV. Among HEC regimens, the incidence of CINV and the degree of nausea on day 1 of anthracycline-cyclophosphamide combination therapy were higher than with a cisplatin-based regimen. CONCLUSIONS: Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed nausea in HEC and MEC patients. Identification of individual risk factors, such as female sex, will assist in the development of personalized treatments for CINV. More intensive antiemetic therapy or a different modality of prophylaxis should be considered for the control of acute CINV in an anthracycline-cyclophosphamide regimen.

Changes in the nitric oxide-soluble guanylate cyclase system and natriuretic peptide receptor system in placentas of pregnant Dahl salt-sensitive rats.

AIM: Diminished vasodilator activity during pregnancy, which augments vascular responses to vasoconstrictors, is one reason for the onset of pre-eclampsia and superimposed pre-eclampsia. It is known that Dahl salt-sensitive (Dahl-S) rats develop salt-sensitive hypertension like African-Americans. The present study attempted to assess the changes and the interactions of the NOS-NO-sGC-cGMP and NP-NPR-cGMP systems in the hypertensive placenta using Dahl-S rats as an animal model of superimposed pre-eclampsia. MATERIAL AND METHODS: Pregnant Dahl-S rats were fed a high-salt diet to induce the development of hypertension and fetal growth restriction. Using these rats, we investigated the regulation of these two vasodilatation systems, including the kinetics of cyclic guanosine monophosphate (cGMP), soluble guanylate cyclase (sGC), endothelial nitric oxide synthase (NOS), cytokine-inducible NOS, natriuretic peptides (NP) (atrial NP, brain NP and C-type NP), and NP receptors (NPR) (NPR-A, NPR-B, NPR-C). RESULTS: Dahl-S rats fed a high-salt diet exhibited hypertension, fetal growth restriction and thickening of the walls in decidual vessels. The placental cGMP level in the rats fed the high-salt diet was significantly decreased compared with that in controls. The expression levels of endothelial NOS and cytokine-inducible NOS mRNA increased significantly, while that of sGCα2-sunbnit declined significantly. Messenger RNA levels of NPR-C, a clearance-type receptor of NP, declined significantly, whereas those of NP and their functional receptors NPR-A and NPR-B were unchanged. CONCLUSIONS: As Dahl-S rats with excess salt-loading during pregnancy exhibited pathological changes similar to those observed in female humans with pre-eclampsia/superimposed pre-eclampsia, this rat could be useful as an animal model of superimposed pre-eclampsia. In the placentas of hypertensive Dahl-S rats, vasodilatation seemed to be disturbed by the deregulation of both the NO-sGC-cGMP and NP-NPR-cGMP systems.

Nuclear Y-box-binding protein-1 is a poor prognostic marker and related to epidermal growth factor receptor in uterine cervical cancer.

OBJECTIVE: Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many studies indicate that YB-1 is strongly expressed in tumor cells and is considered a marker of tumor aggressiveness and clinical prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been associated with poor outcomes in cervical cancer. Clinical trials of EGFR family-base therapy are currently being initiated in cervical cancer. Nuclear YB-1 expression correlates with EGFR expression in various types of cancer. However, the clinical significance of nuclear YB-1 expression in different settings, the correlation with EGFR, and the prognostic implications of YB-1 expression in cervical cancer remain elusive. PATIENTS AND METHODS: Nuclear YB-1 expression was immunohistochemically analyzed in tissue specimens obtained from 204 patients with cervical cancer who underwent surgery. Associations of nuclear YB-1 expression with clinicopathological factors such as survival, EGFR expression, and human epidermal growth factor receptor 2 (HER2) expression were investigated. RESULTS: Nuclear YB-1 expression was found in 41 (20.2%) of 204 cases of cervical cancer and correlated with disease stage, tumor diameter, stromal invasion, and lymph-node metastasis. Nuclear YB-1 expression also correlated with EGFR expression (P=0.0114) as well as HER2 expression (P=0.0053). Kaplan-Meier survival analysis showed that nuclear YB-1 expression was significantly associated with poor progression-free survival (P=0.0033) and overall survival (P=0.0003), respectively. CONCLUSION: Nuclear YB-1 expression is a prognostic marker and correlates with EGFR expression in cervical cancer.

Validity of intraoperative diagnosis at laparoscopic surgery for ovarian tumors.

STUDY OBJECTIVE: To evaluate the accuracy and usefulness of intraoperative diagnosis of ovarian tumor during laparoscopic surgery. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Tertiary care university hospital. PATIENTS: We reviewed the cases of 262 patients who underwent laparoscopic surgery at our institution between January 2005 and December 2011 in whom a benign ovarian tumor was diagnosed intraoperatively. INTERVENTIONS: Intraoperative pathologic assessment of frozen sections. MEASUREMENTS AND MAIN RESULTS: Intraoperative diagnosis of ovarian tumors demonstrated sensitivity of 80%, specificity of 99.6%, positive predictive value of 80%, and diagnostic accuracy of 99.2%. Mucinous tumors diagnosed intraoperatively showed differing intraoperative and final pathologic diagnoses significantly more frequently than did other types of tumors. CONCLUSION: Intraoperative pathologic assessment of benign ovarian tumors during laparoscopic surgery is reliable. However, clinicians should recognize that it is possible to make an incorrect diagnosis in some situations and should exercise caution accordingly.

Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients.

CONTEXT: To develop a personalized peptide vaccine (PPV) for recurrent ovarian cancer patients and evaluate its efficacy from the point of view of overall survival (OS), Phase II study of PPV was performed. PATIENTS AND METHODS: Forty-two patients, 17 with platinum-sensitive and 25 with platinum-resistant recurrent ovarian cancer, were enrolled in this study and received a maximum of four peptides based on HLA-A types and IgG responses to the peptides in pre-vaccination plasma. RESULTS: Expression of 13 of the 15 parental tumor-associated antigens encoding the vaccine peptides, with the two prostate-related antigens being the exceptions, was confirmed in the ovarian cancer tissues. No vaccine-related systemic severe adverse events were observed in any patients. Boosting of cytotoxic T lymphocytes or IgG responses specific for the peptides used for vaccination was observed in 18 or 13 of 42 cases at 6th vaccination, and 19 or 29 of 30 cases at 12th vaccination, respectively. The median survival time (MST) values of the platinum-sensitive- and platinum-resistant recurrent cases were 39.3 and 16.2 months, respectively. The MST of PPV monotherapy or PPV in combination with any chemotherapy during the 1st to 12th vaccination of platinum-sensitive cases was 39.3 or 32.2 months, and that of platinum-resistant cases was 16.8 or 16.1 months, respectively. Importantly, lymphocyte frequency and epitope spreading were significantly prognostic of OS. DISCUSSION AND CONCLUSION: Because of the safety and possible prolongation of OS, a clinical trial of PPV without chemotherapy during the 1st to 12th vaccination in recurrent ovarian cancer patients is merited.

Status of treatment for the overall population of patients with stage IVb endometrial cancer, and evaluation of the role of preoperative chemotherapy: a retrospective multi-institutional study of 426 patients in Japan.

OBJECTIVE: We previously reported on the role of cytoreduction in 248 patients with surgical stage IVb endometrial cancer (EMCA). This study aimed to evaluate the clinical characteristics, prognosis according to initial treatment, and impact of preoperative chemotherapy in the overall population of patients with clinical and surgical stage IVb EMCA. METHODS: A multi-institutional retrospective analysis was performed in 426 patients diagnosed with clinical and surgical stage IVb EMCA from 1996 to 2005. Factors associated with overall survival (OS) were identified using univariate and multivariate analyses. RESULTS: The median OS for all 426 patients was 14 months. Patients were divided into three groups according to their initial treatment: primary surgery group (n=279), primary chemotherapy group (n=125), and palliative care group (n=22). The median OS times for these groups were 21, 12, and 1 month, respectively (p<0.0001). Patients in the primary surgery group had better performance status (PS) and lower numbers of extra-abdominal metastases than those in the primary chemotherapy group. Multivariate analysis identified good PS, endometrioid histology, absence of clinical intra-abdominal stage IVb metastasis, hysterectomy, and chemotherapy as independent predictors of OS. In the primary chemotherapy group, 59 patients subsequently underwent surgery, and these patients had similar OS to those in the primary surgery group. CONCLUSIONS: Hysterectomy and chemotherapy may prolong OS in selected patients with stage IVb EMCA. Our data suggest that primary chemotherapy followed by surgery may be a useful treatment choice in patients not suitable for primary surgery.

Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study.

BACKGROUND: The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment. PATIENTS AND METHODS: Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m(2) (day 1) and irinotecan 60 mg/m(2) (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease. RESULTS: Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild. CONCLUSION: Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival.

Fetomaternal hemorrhage with intraplacental chorioangioma.

A 37-year-old Asian woman, gravid 0 para 0, was admitted to our hospital at 34 weeks and 5 days of her pregnancy for management of preeclampsia. A few days after admission, she recognized diminished fetal movement, and a non-stress test revealed a non-reassuring fetal heart rate pattern with decreased variability. A female baby weighing 1840 g was delivered by emergency cesarean section with Apgar scores of 5 and 5 at 1 and 5 min, respectively. Significant neonatal anemia with a hemoglobin level of 4.3 g/dL was observed. The elevated level of hemoglobin F (HbF) in the maternal blood accounted for 4.6% (normal≦0.5%), and was indicative of the presence of fetomaternal hemorrhage (FMH). Microscopic examination of the placenta revealed chorioangioma. We report here a rare case of FMH with intraplacental chorioangioma, and discuss the relationship between these two pathologies.

[A patient with recurrent ovarian clear cell adenocarcinoma and chronic kidney disease exhibited complete response to paclitaxel plus carboplatin].

A 41-year-old woman receiving hemodialysis 3 times a week for chronic kidney disease caused by interstitial nephritis was referred to our hospital because of a pelvic mass and subsequently underwent primary surgery. The patient was diagnosed with FIGO stage Ic (b) clear cell adenocarcinoma. She did not receive postoperative chemotherapy. However, 9 months after surgery, ascites and a pelvic mass developed, on the basis of which recurrence was confirmed. She received combination chemotherapy with paclitaxel plus carboplatin (TC). Paclitaxel was administered at 175 mg/m2, and the carboplatin dosage was calculated by the Calvert formula. The glomerular filtration rate was considered to be 0, and the target area under the plasma concentration versus time curve was 5. Hemodialysis was performed 24 hours after the infusion of carboplatin. After 6 courses of combination chemotherapy, complete response was confirmed by computed tomography. The patient developed grade 3 neutropenia, grade 1 sensory neuropathy , and grade 2 alopecia, but the other adverse events were mild. In conclusion, TC combination chemotherapy was well tolerated and generated a good response in a patient with recurrent ovarian clear cell adenocarcinoma who was receiving hemodialysis for chronic kidney disease.

[Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on platinum-sensitive recurrent epithelial ovarian cancer].

OBJECTIVE: We evaluated the safety and efficacy of pegylated liposomal doxorubicin(PLD)and carboplatin(CBDCA)(CD) for platinum-sensitive recurrent epithelial ovarian cancer. METHODS: From December 2010 to June 2011, 9 eligible patients with histologically confirmed, recurrent epithelial ovarian cancer, which was deemed platinum-sensitive, were enrolled onto the study. PLD(30mg/m2)and CBDCA(area under the curve[AUC]5)were administered intravenously on day 1 of the cycle. The chemotherapy regimen was repeated every 4 weeks, until disease progression or completion of 6 cycles. RESULTS: A total of 49 treatment cycles of CD were administered to 9 patients. The median platinum-free interval was 18.3 months. Patients with Grade 3/4 hematological toxicities were observed to have leucopenia(11.1%), neutropenia(44.4%), anemia (22.2%), and thrombocytopenia (22.2%). No Grade 3/4 non-hematological toxicities were observed, and no treatment related death occurred. Seven patients(77.7%)responded to CD(4 complete responses and 3 partial responses). The median progression-free survival and overall survival times were 15.1 and 23.7 months. CONCLUSION: CD treatment seems to be a safe and effective chemotherapy regimen for platinum-sensitive recurrent epithelial ovarian cancer.

Identification of B cell epitopes reactive to human papillomavirus type-16L1- derived peptides.

BACKGROUND: Persistent infection of human papillomavirus (HPV) types 16 and 18 causes cervical cancer. To better understand immune responses to the prophylactic vaccine, HPV 16/18 L1 virus-like particles (HPV-VLPs), we investigated B cell epitopes of HPV16 L1-derived peptides. METHODS: Sera from mice immunized with HPV-16/18 L1 VLPs were analyzed for their IgG titers against 10 different HPV16 L1-derived peptides (20-mer) that contain human leukocyte antigen (HLA)-class I A-2, A-24 and class II DR. RESULTS: One 20-mer peptide at positions 300 to 319 was identified as a common B cell epitope in both Balb/c (H-2d) and C57BL/6 (H-2b) mice. Mapping analysis showed that the 10-amino-acid sequence at positions 304 to 313 was an immunogenic portion. It is of note that the binding capability of this 10-mer peptide to the HLA-A2 and HLA-A24 molecules was confirmed by the HLA class I stabilization assay. In addition, one unique 20-mer was determined as a B cell epitope in each strain. CONCLUSIONS: These results might provide new information for better understanding of immune responses to HPV 16 L1.

A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer.

OBJECTIVE: The aim of this prospective trial was to evaluate the efficacy and safety of the combination of paclitaxel and carboplatin (TC) in patients with metastatic or recurrent cervical cancer. METHODS: This was a multicenter phase II trial of 3 weekly paclitaxel 175 mg/m(2) 3-hour iv day 1 followed by carboplatin AUC5 1-hour iv day 1 for maximum of 6 cycles until disease progression or prohibitive toxicity. Eligible patients had squamous or adenocarcinoma of the cervix with measurable stage IVB or recurrent, aged 20-75 years, Eastern Cooperative Oncology Group performance status 0-2, prior platinum-containing regimen 0-1, and no prior taxane. The primary endpoint was overall response rate (ORR) by RECIST. RESULTS: 41 patients were enrolled, of which 39 were evaluable for analysis. 33 patients (84.6%) received prior radiotherapy. The confirmed ORR was 59% (95% CI, 43% to 75%); 5 patients (13%) achieved a complete response and median response duration was 5.2 months. The response rates for patients who had adenocarcinoma (n=10) and prior platinum-based chemotherapy<6 months (n=7) were 40.0% and 0%, respectively. The median progression-free survival and overall survival times were 5.3 and 9.6 months, respectively. The most frequent grade 3 or 4 adverse events were neutropenia (79%), anemia (46%), thrombocytopenia (15%), and fatigue (8%). No treatment-related death was seen. CONCLUSIONS: TC seemed to be feasible and effective similar to other cisplatin-based doublets for the treatment of metastatic or recurrent cervical cancer. Phase III trial is warranted to establish the clinical benefits of this combination.