[Show abstract][Hide abstract] ABSTRACT: Human epididymis protein 4 (HE4) levels and the Risk of Ovarian Malignancy Algorithm (ROMA) have recently been shown to improve the sensitivity and specificity of epithelial ovarian cancer (EOC) diagnosis. We evaluated HE4 levels and ROMA as diagnostic tools of type I and type II EOC in Japanese women. Women who had a pelvic mass on imaging and were scheduled to undergo surgery were enrolled as ovarian mass patients. Serum levels of carbohydrate antigen 125 (CA125) and HE4 were tested in 319 women (131 benign, 19 borderline, 75 malignant, and 94 healthy controls). CA125, HE4, and ROMA were evaluated for sensitivity and by receiver operating characteristics (ROC) in type I and type II EOC. The results showed that, at 75 % specificity, the sensitivity of CA125 and HE4 for type II was 92.1 % for both markers and for type I was 51.5 % and 78.8 %, respectively. The sensitivities of ROMA (type I, 84.8 % and type II, 97.4 %) were better than those of CA125 and HE4. CA125, HE4, and ROMA were all highly accurate markers for type II. For type I, HE4 and ROMA showed better sensitivity than CA125. ROMA displayed the best diagnostic power for type I and type II including for the early stage of type I. In conclusion, HE4, CA125, and ROMA are valuable markers for type II EOC diagnosis. HE4 and ROMA analyses may improve differentiation between type I EOC and a benign mass. Measurement of combined HE4 and CA125 levels provides a more accurate method for EOC diagnosis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the current operative management of International Federation of Gynecology and Obstetrics (FIGO) stage IB2, IIA2, and IIB uterine cervical cancer (bulky tumors) in Japan by surveying the member institutions of the Japanese Gynecologic Oncology Group.
International Journal of Gynecological Cancer 07/2014; · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although recurrent epithelial ovarian cancer (EOC) is generally regarded as an incurable disease, some patients survive more than 5 years after the first recurrence. The aim of this study was to evaluate the clinical features of patients with recurrent EOC who achieve long-term survival.
We retrospectively reviewed the medical records of 164 patients with recurrent EOC and analyzed the clinical stage, histologic subtype, primary treatment, disease-free interval (DFI), recurrence site, secondary treatment, and overall survival from the time of the first recurrence (R-OS), using the Kaplan-Meier method and the log-rank test.
The median R-OS for all 164 patients was 25 months and the 5-year R-OS rate was 25.4 %. There were no significant differences in R-OS according to the disease stage. The median R-OS was significantly shorter in the 6-12-month DFI group (23 months) than in the ≥12-month DFI group (61 months) (p = 0.0002), while there was no significant difference between the 6-12 and 3-6-month DFI groups (20 months) (p = 0.161). Of the 164 patients, only 14 survived >5 years after the first recurrence. Most of them underwent surgery and/or radiotherapy in combination with chemotherapy and underwent >18 cycles of platinum-based chemotherapy throughout their treatments (median 22 cycles; range 4-44).
If high sensitivity to platinum is maintained, patients with recurrent EOC may have prolonged survival following repeated platinum-based chemotherapy cycles. Moreover, their prognosis improves when chemotherapy is combined with secondary cytoreductive surgery and/or irradiation.
International Journal of Clinical Oncology 03/2014; · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:
The objective of this study was to determine the current operative principle of uterine cervical cancer of stages Ia2, Ib1, and IIa1 (International Federation of Gynecology and Obstetrics) in Japan by surveying member institutions of the Japanese Gynecologic Oncology Group (JGOG).
We conducted a survey to assess the current operative principle, including indications and treatment, at all 199 active member institutions of the JGOG.
A total of 166 institutions (83.4%) responded to the survey. For Ia2 squamous cell carcinoma without the need to preserve fertility, modified radical hysterectomy was performed, and lymph node dissection was done in about 85%. At 60% of JGOG institutions, it was considered that less invasive procedures might be suitable. At the majority of JGOG institutions, radical surgery and lymph node dissection were considered necessary for stages Ib1 and IIa1 squamous cell carcinoma, with 70% considering that less invasive procedures might not be suitable.
This survey provides information regarding the current status of surgical principle for uterine cervical cancer (stages Ia2, Ib1, and IIa1) in Japan.
International Journal of Gynecological Cancer 11/2013; 23(9):1655-62. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few studies have examined the effect of combined low-risk human papillomavirus (LR-HPV) and high-risk human papillomavirus (HR-HPV) infection on the progression of cervical intraepithelial neoplasia (CIN)2 to CIN3. This multi-institutional prospective cohort study investigated the risk of progression of CIN2 with various combinations of HR-HPV and LR-HPV infection.
Between January 2007 and May 2008, 122 women with CIN2 (aged 20-50 years) from 24 hospitals throughout Japan were enrolled in the study. Ninety-three women were analyzed after a 2-year follow-up with cytology, colposcopy, HR-HPV testing and HPV genotyping. Colposcopy-directed biopsy was performed at entry and the end of this study, or when disease progression was suspected.
Among 93 women with CIN2, 87 (93.5%) had HR-HPV infection. Among these 87 cases, 24 (27.6%) progressed to CIN3 and 49 (56.3%) regressed. None of the six women with CIN2 without HR-HPV infection progressed. The progression rate was significantly lower in women with combined HR-HPV and LR-HPV infection (3/28, 10.7%) than in those with HR-HPV infection only (21/59, 35.6%; P = 0.016). Multivariate analyses showed that CIN2 progression in women with HR-HPV infection was negatively associated with LR-HPV co-infection (hazard ratio = 0.152; 95% confidence interval [CI] = 0.042-0.553). CIN2 regression was positively associated with LR-HPV co-infection (odds ratio = 4.553; 95% CI = 1.378-15.039).
The risk of CIN2 progression is low in women with combined infection of HR-HPV and LR-HPV. The finding may be useful for management of women diagnosed with CIN2.
Journal of Obstetrics and Gynaecology Research 10/2013; · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the clinical performance of the Amplicor HPV test, which detects 13 high-risk human papillomaviruses (HR-HPV), and to determine the association between consistent HR-HPV infection and progression of cervical intraepithelial neoplasia (CIN) 2 to CIN3.
This multi-institutional prospective study enrolled 122 women diagnosed with CIN2 by central pathological review. Subjects were tested at study entry and every 6 months over a 24-month period by cytology, Amplicor HPV test and colposcopy. Central pathological review was performed at the end of the study or if CIN progression was suspected.
Ninety-three of the 122 participants completed all tests in the study and were included in the analysis. HR-HPV was detected in 87/93 (93.5%) participants at study entry. Twenty-four of the 87 HR-HPV-positive participants progressed to ≥CIN3, compared with none of the six participants who were HR-HPV-negative at study entry. The positive predictive value, negative predictive value, sensitivity and specificity of the Amplicor HPV test at study entry for predicting ≥CIN3 progression were 27.6%, 100%, 100% and 8.7%, respectively. Sixty-two participants were HR-HPV-positive from study entry through to study completion, 24 of whom progressed to ≥CIN3. None of 31 participants without continuous HR-HPV detection progressed to ≥CIN3. For continuous HR-HPV detection, the positive predictive value, negative predictive value, sensitivity and specificity of the Amplicor HPV test were 38.7%, 100%, 100% and 44.9%, respectively.
All participants who progressed to ≥CIN3 were continuously HR-HPV-positive. The Amplicor HPV test thus demonstrated a good performance for predicting CIN3 progression.
Journal of Obstetrics and Gynaecology Research 07/2013; · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To assess the feasibility and acute toxicity of concurrent chemoradiotherapy (CCRT) with high-dose rate intracavitary brachytherapy (HDR-ICBT) and standard dose delivery of cisplatin for Japanese patients with cervical cancer. MATERIALS AND METHODS: The phase 2 study included Japanese patients with International Federation of Gynecology and Obstetrics stage III to IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by computed tomography. Patients were 20 to 70 years of age and had Eastern Cooperative Oncology Group performance status of 0 to 1. The radiotherapy protocol consisted of whole-pelvis external beam radiotherapy and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62 to 65 Gy prescribed at point A. Cisplatin was administered weekly at a dose of 40 mg/m for 5 courses. RESULTS: Between March 2008 and January 2009, 72 patients from 25 institutions were enrolled, and 71 patients were eligible and evaluable for compliance and severe toxicity. The median age of the patients was 57 years (range, 32-70 years). Sixty-five patients (92%) received the planned 5 courses of chemotherapy. Four patients had cisplatin dose reduction according to the protocol. Radiotherapy was completed per protocol in 68 patients (96%). Median overall treatment time was 50 days (range, 37-66 days). The following grade 3 or 4 acute adverse events were observed: neutropenia in 31 patients (44%), anemia in 10 patients (14%), diarrhea in 4 patients (6%), and anorexia in 3 patients (4%). CONCLUSIONS: Concurrent chemoradiotherapy with HDR-ICBT and standard weekly delivery of cisplatin was feasible with acceptable toxicity in Japanese patients with cervical cancer.
International Journal of Gynecological Cancer 08/2012; 22(8):1420-1426. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma. Eligibility included patients who received irinotecan (60 mg/m2) on days 1 and 8 and nedaplatin (80 mg/m2) on day 1 of a 21-day cycle. After 1-3 courses of chemotherapy, radical hysterectomy was performed. Sixty-eight patients were enrolled. Sixty-six were included in the full analysis set. Their median age was 47 years (range 22-71), the FIGO stage was Ib2 in 18 patients, IIa in 10, and IIb in 38. Radical hysterectomy was performed after NAC in 63 patients (95.5%). The number of administered courses of NAC was 1 in 13 patients, 2 in 43, and 3 in 10. The response rate, the primary endpoint of this study, was 75.8% (CR in 2 patients, PR in 48, SD in 12, PD in 0, and NE in 4). The mean number of treatment courses required for a response was 1.42 (1 course in 30 patients, 2 courses in 19, and 3 courses in 1). The incidences of grade 3 or 4 hematological toxicities were: neutropenia 72.2%, leukopenia 16.7%, anemia 13.6%, thrombocytopenia 7.6%, febrile neutropenia 1.5%, and elevations of alanine aminotransferase and aspartate aminotransferase 1.5%. Grade 3 or 4 non-hematologic toxicities were as follows: diarrhea 6.1%, nausea 3%, anorexia 1.5%, vomiting 1.5%, fever 1.5%, allergic reactions 1.5%, ileus 1.5% and vesicovaginal fistula 1.5%. Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix.
[Show abstract][Hide abstract] ABSTRACT: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with high-dose-rate intracavitary brachytherapy (HDR-ICBT) using a low cumulative prescribed dose schedule in patients with locally advanced uterine cervical cancer.
The Japanese Gynecologic Oncology Group (JGOG) study JGOG1066 enrolled patients with FIGO stages III-IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by CT. Patients received definitive radiotherapy (RT) consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62-65 Gy prescribed at point A. Cisplatin 40 mg/m(2) weekly was administered concurrently with RT for 5 courses.
Of the 72 patients registered, 71 were eligible. With a median follow-up of 28 months, the 2-year progression-free survival rate and pelvic disease progression-free rate were 66% (95% CI, 54% to 76%) and 73% (95% CI, 61% to 82%), respectively. Progression-free survival decreased significantly with increased central tumor size (P=0.036). The 2-year cumulative late complication rates were 24% for all grades, 9% for grade 1, 12% for grade 2, 3% for grade 3, and 0 for grades 4/5.
The JGOG1066 demonstrated that CCRT using HDR-ICBT with a low cumulative RT dose schedule achieved comparable outcome as those achieved with global dose schedules (EQD2=85 Gy) with a lower incidence of late toxicity for locally advanced uterine cervical cancer in a Japanese population.
[Show abstract][Hide abstract] ABSTRACT: In Japan, awareness of hereditary breast and ovarian cancer (HBOC) has gradually increased among health care workers and the general population. We focus on two current topics: genetic testing and risk-reducing surgery for HBOC. Genetic testing for BRCA1 and BRCA2, the genes responsible for HBOC, is performed to diagnose HBOC. PCR-direct sequencing is a standard method used for BRCA1/2 mutation analysis. Recently, genetic rearrangement of BRCA1 was reported in a Japanese patient with HBOC. Therefore, MLPA tests are also being included in routine genetic testing for the disease. The result of "uncertain significance, " which indicates unclear pathogenic significance, is obtained in about 3% of all patients who undergo BRCA1/2 genetic tests. Furthermore, novel candidate genes for HBOC, such as RAD51C, PALB2, and BRIP1, were recently identified. Prophylactic surgical intervention for HBOC includes procedures such as risk-reducing bilateral salpingo-oophorectomy (RRSO) and risk-reducing mastectomy(RRM). In Japan, RRSO is performed in very few patients at present. Increasing evidence from overseas indicates that RRSO contributes to a decreased incidence of ovarian/breast cancers and lowers overall mortality. Therefore, a system for performing RRSO was established in our institute. RRSO was approved to be performed as a clinical examination by our Institutional Review Board. The clinical significance of ipsilateral complete mastectomy and RRM remains unclear. Based on the NCCN guidelines, conservative mastectomy with radiation therapy is relatively contraindicated in patients with HBOC. However, several studies have reported that conservative mastectomy with radiation the rapydoes not increase the incidence of recurrent or metachronous breast cancers in the ipsilateral breast of mutation-positive patients when compared to mutation-negative or control patients. However, more aggressive malignancies seem to be included in the mutation-positive group(especially BRCA1 -mutation-positive cases). RRM clearly reduced the incidence of breast cancers. RRM may also be allowed as a treatment option for HBOC in Japan.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2012; 39(4):525-31.
[Show abstract][Hide abstract] ABSTRACT: Although postoperative adjuvant chemotherapy is generally recommended for early-stage ovarian cancer, it remains unclear whether adjuvant chemotherapy is also effective for clear cell carcinoma (CCC).
Seventy-three patients with stage I CCC of the ovary who had undergone complete surgical staging formed the study population (stage IA, 20 patients; stage IC, 53 patients). Survival and multivariate analyses were retrospectively performed to determine the effectiveness of postoperative chemotherapy in these patients.
Of the total (73 patients), 30 patients received adjuvant chemotherapy (stage I C-positive), whereas 43 patients did not (stage I C-negative). The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates for the stage I C-positive group were 80.1% and 87.4% compared with 73.9% and 81.7% for the stage I C-negative group. The differences in survival between these groups were not significant (PFS: P = 0.610; OS: P = 0.557). Four of the patients with stage IA CCC underwent chemotherapy, whereas the remaining 16 patients received no additional therapy. No recurrence was observed in either group. Of the patients with stage IC CCC, 26 patients underwent chemotherapy (stage IC C-positive) and 27 received no additional therapy (stage IC C-negative). There was no statistical difference in PFS and OS between the stage IC C-positive and stage IC C-negative groups. Of the patients with stage IC without artificial rupture, the 5-year PFS rates of the C-positive and C-negative patients were 69.6% and 34.6%, respectively, but the 5-year OS rates were 75.0% and 70.0%, respectively (not significant). Multivariate analyses confirmed that the presence or absence of adjuvant chemotherapy was not a prognostic indicator.
The current study was performed only in fully staged patients, suggesting that postoperative adjuvant chemotherapy is not necessary for stage IA CCC patients. For patients with stage IC CCC patients, adjuvant chemotherapy suppressed recurrence, but the effectiveness was insufficient in our limited study. Further studies are required to clarify this.
International Journal of Gynecological Cancer 03/2012; 22(4):573-8. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the safety and usefulness of conization with an electrosurgical loop (the loop electrosurgical excision procedure [LEEP]) in young women with carcinoma in situ (CIS) of the uterine cervix.
A retrospective medical chart review of five patients with CIS initially treated with LEEP conization between 2002 and 2010 and who later experienced recurrence in the form of invasive or advanced disease was conducted.
The median patient age at initial LEEP conization was 41years (33-56years). The margin status in conization specimens was positive in three of the five patients. The median time to detection of tumor progression was 50months (17-58months). Magnetic resonance imaging was effective in detecting tumor recurrence in all cases. In four patients, hysterectomy was performed to treat the recurrence; these four patients are currently alive and disease-free. One patient with cervical lymph nodes and bone metastases was treated with chemotherapy alone; however, the patient died. In surgical specimens, tumor progression was observed extending toward the endometrium in all five patients and toward the vagina in two patients.
This study indicates that patients with CIS occasionally show unexpected tumor progression after conization and the progression could be life-threatening. Recurrent disease often shows tumor progression toward the endometrium or vagina, leading to difficulties in its detection at periodic pelvic examinations.
Journal of Obstetrics and Gynaecology Research 09/2011; 38(1):84-8. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to compare sonographic findings and histopathologic types of stage IA ovarian cancers between groups with normal and elevated cancer antigen 125 (CA-125) levels.
Between 2000 and 2009, 146 stage IA ovarian cancers were treated surgically (85 invasive and 61 borderline, 73 self-referred with tumor-related symptoms, 20 self-referred with nonspecific symptoms, 52 identified through screening, and 1 other). Of these, 87 cases (60%) had normal serum CA-125 levels (<35 U/mL). Their pre-operative sonographic findings and histopathologic types were compared to those of cases with elevated CA-125 levels.
Statistically significant differences were found between the proportions of patients with elevated CA-125 levels in groups having tumors with maximal diameters of less than 20 cm and at least 20 cm (P = .03) and groups having tumors with less than 50% and 50% to 80% solid components (P = .02). In the group with normal CA-125 levels, we found predominantly mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (25 cases), and clear cell adenocarcinoma in unilocular cysts with less than 50% solid components (12 cases), whereas in the group with elevated CA-125 levels, mucinous adenocarcinoma in multilocular cysts with less than 50% solid components (19 cases) and endometrioid adenocarcinoma in solid tumors (≥80% solid components) were predominant (5 cases).
Stage IA ovarian cancers with normal CA-125 levels tend to be smaller, have less solid components, and have a slightly different distribution of histopathologic types than cancers with elevated CA-125 levels.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 07/2011; 30(7):943-52. · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess radiotherapy protocol compliance in a multi-institutional phase II study of concurrent chemoradiotherapy for patients with locally advanced cancer of the uterine cervix (JGOG1066).
For study protocol development, various radiotherapy parameters were examined and consensus was reached by Japanese radiation oncologists with cervical cancer treatment expertise. Quality assurance (QA) was also discussed and included in the protocol. A credentialing process was used to select institutions for participation in the study. Individual case reviews referring to 18 QA items were undertaken for each patient. Radiotherapy data were submitted to the Japanese Gynecologic Oncology Group (JGOG) data center and reviewed by the members of the radiotherapy committee. The QA evaluation was classed as per protocol, deviation, and violation.
Individual case reviews were performed on 69 of 72 patients entered in the study. In 24 patients (35%), there were no deviations for any QA items. There were also no deviations seen for 5 of the 18 items in 69 patients evaluated. Deviations of 64 QA items were seen in 45 cases, and violations were seen in 4 cases (4 items). The most common deviation concerned appropriate application for the external beam radiotherapy (EBRT) boost to involved nodes or parametrium (32 cases). The 4 violations were identified in the QA items regarding high-dose rate intracavitary brachytherapy.
Radiotherapy protocol compliance was favorable except for the EBRT boost indications. The results of this study validate the quality of radiotherapy in JGOG1066, and indicate that the final analysis will provide meaningful results.
International Journal of Clinical Oncology 02/2011; 16(4):379-86. · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: In the surgical treatment for early-stage cervical carcinoma, it is important to identify preoperatively a low-risk group of patients as candidates for less radical surgery to avoid the morbidity associated with radical hysterectomy. The aim of this study was to evaluate the correlation between tumor diameter measured preoperatively using magnetic resonance imaging (MRI) and pathological prognostic factors in International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical carcinoma.Methods: A total of 125 patients with FIGO stage IB1 cervical cancer were included in this study. Clinical records, pathology reports, and MRI findings were retrospectively reviewed.Results: Histological diagnosis was squamous cell carcinoma in 57 patients and non squamous cell carcinoma in 68 patients. All patients underwent preoperative evaluation by MRI within a median period of 13.5 days before surgery. The tumor diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a median of 23 mm.Pathological prognostic factors included parametrial involvement, lymph node metastasis,deep stromal invasion, and lymphovascular space invasion. All these factors were found less frequently in patients with a smaller tumor diameter. Most notably, parametrial involvement was seen in none of the patients with tumors 20 mm or less and was detected only in patients with tumors greater than 20 mm (P = 0.01).Conclusions: In the FIGO stage IB1 cervical carcinoma, the tumor diameter measured preoperatively by MRI correlates well with other pathological prognostic factors, especially with parametrial involvement. This finding suggests that the tumor diameter measured in preoperative MRI may serve as a strong predictor of parametrial involvement in FIGO stage IB1 cervical carcinoma, which can be used to select a candidate population for less radical surgery without the need for a cone biopsy before hysterectomy.
International Journal of Gynecological Cancer 02/2011; 21(2):349-54. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate clinical outcomes with respect to the effectiveness of chemotherapy in the treatment of uterine leiomyosarcoma.
Study subjects were 18 patients with uterine leiomyosarcoma treated surgically at our hospital between February 1986 and December 2007. A chemotherapy regimen that combined ifosfamide, epirubicine, and cisplatin (IEP) was used as the main first-line chemotherapy.
FIGO disease stages were as follows: Stage I (n = 11), Stage II (n = 1), Stage III (n = 3), Stage IV (n = 3). Five-year overall survival of patients with Stage I-III disease was 65.3% (95% CI: 46.1-92.4%). None of patients with Stage IV disease survived for more than two years. Of seven patients who suffered advanced or recurrent disease, six received IEP; the response rate was 50%, one complete response and two partial responses.
The combination of surgery and chemotherapy seems to be an acceptable treatment for uterine leiomyosarcoma. IEP may be an active regimen for this aggressive disease.
European journal of gynaecological oncology 01/2011; 32(6):647-50. · 0.60 Impact Factor