Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Current Status of Uterine Leiomyosarcoma in the Tohoku Region: Results of the Tohoku Translational Center Development Network Survey.

BACKGROUND: To prepare for a future clinical trial for improving the long-term prognosis of patients with uterine leiomyosarcoma (ULMS), we conducted a multi-institutional survey in the Tohoku region of Japan. METHODS: We conducted a retrospective cohort study between 2011 and 2014 in member institutions of the Tohoku Translational Research Center Development Network. RESULTS: A total of 53 patients with ULMS were registered in 31 institutions for the present survey. The median patient age was 56 years, 67.9% of the patients were postmenopausal, 88.7% had a performance status of 0 or 1, and only 6 patients (11.3%) showed preoperative evidence of malignancy. Although retroperitoneal lymphadenectomy was performed in only 26.4% of patients, 64.2% patients were identified as having FIGO stage 1 disease; 73.6% were eligible to undergo complete surgery. Among 36 patients who were treated with postoperative chemotherapy, 28 (77.8%) received docetaxel and gemcitabine combination therapy. The most frequent recurrence site was the lungs, and the median progression-free survival of all enrolled patients was 11.7 months. However, the median progression-free survival and the median overall survival in patients with stages III and IV disease were 3.4 and 11.4 months, respectively. CONCLUSION: Although ULMS was associated with a high rate of complete or optimal surgery, the long-term prognosis was poor. Effective postoperative therapy should be developed to improve the long-term prognosis of patients with ULMS.

Evaluation of postoperative chemotherapy in patients with uterine carcinosarcoma: a retrospective survey of the Tohoku Gynecologic Cancer Unit.

BACKGROUND: The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma. METHODS: We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit. RESULTS: A total of 45 patients who had undergone hysterectomy and bilateral salpingo-oophorectomy were enrolled. No significant difference was observed in overall survival according to patient age (≤ 50 years vs >50 years) or retroperitoneal lymphadenectomy (performed vs. not performed). However, the International Federation of Gynecology and Obstetrics stage (stage I/II vs stage III/IV) and postoperative chemotherapy (provided vs not provided) were significant prognostic factors in both univariate and multivariate analyses for the 25-month median follow-up period. CONCLUSIONS: Our results revealed that postoperative chemotherapy should be considered for all uterine carcinosarcoma stages in Japanese patients.

Efficacy and safety of triple therapy with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy for gynecological cancer: KCOG-G1003 phase II trial.

PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)). METHODS: Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy). RESULTS: Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each). CONCLUSIONS: Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.

Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer.

BACKGROUND: Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival. METHODS: We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011. RESULTS: Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred. CONCLUSIONS: Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

Feasibility study of gemcitabine plus docetaxel in advanced or recurrent uterine leiomyosarcoma and undifferentiated endometrial sarcoma in Japan.

BACKGROUND: Uterine leiomyosarcoma (LMS) and undifferentiated endometrial sarcoma (UES) are rare, aggressive malignancies. Both are treated similarly; however, few chemotherapy agents are effective. Recently, the combination of gemcitabine (900 mg/m(2), days 1 and 8) plus docetaxel (100 mg/m(2), day 8) with granulocyte colony-stimulating factor (G-CSF, 150 µg/m(2), days 9-15) has been shown to have activity in LMS. In Japan, neither prophylactic G-CSF at a dose of 150 µg/m(2) nor docetaxel at a dose of 100 mg/m(2) are approved for use. For this reason, we evaluated the combination of 900 mg/m(2) gemcitabine plus 70 mg/m(2) docetaxel regimen without prophylactic G-CSF support in advanced or recurrent LMS and UES in Japanese patients. METHODS: Eligible women with advanced or recurrent LMS and UES were treated with 900 mg/m(2) gemcitabine on days 1 and 8, plus 70 mg/m(2) docetaxel on day 8, every 3 weeks. The primary endpoint was overall response rate, defined as a complete or partial response. RESULTS: Of the eleven women enrolled, 10 were evaluated for a response. One complete response and 2 partial responses were observed (30 %) with an additional 4 (40 %) having stable disease. Mean progression-free survival was 5.4 months (range 1.3-24.8 months), and overall survival was 14 months (range 5.3-38.4 months). Grade 4 neutropenia was the major toxicity (50 %). The median number of cycles was 5 (range 2-18). Twenty-two cycles (44 %) employed G-CSF. CONCLUSION: The gemcitabine plus docetaxel regimen without prophylactic G-CSF support was tolerable and highly efficacious in Japanese patients with advanced or recurrent LMS and UES.

Paclitaxel-carboplatin for advanced or recurrent carcinosarcoma of the uterus: the Japan Uterine Sarcoma Group and Tohoku Gynecologic Cancer Unit Study.

BACKGROUND: Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. METHODS: We conducted a phase II study in which patients were administered paclitaxel 175 mg/m(2) over a 3-h period followed by carboplatin (area under the serum concentration-time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. RESULTS: Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48-77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2-7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. CONCLUSION: This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

Efficacy and safety of bivalent RSVpreF maternal vaccination to prevent RSV illness in Japanese infants: Subset analysis from the pivotal randomized phase 3 MATISSE trial.

BACKGROUND: Maternal vaccination with respiratory syncytial virus prefusion F vaccine (RSVpreF) is effective at preventing RSV-associated lower respiratory tract illness (LRTI) in newborns/infants. METHODS: This subgroup analysis from the global, phase 3, randomized, double-blind, placebo-controlled MATISSE (Maternal Immunization Study for Safety and Efficacy) trial evaluated participants enrolled in Japan. Pregnant women 24-36 weeks' gestation were randomized 1:1 to receive RSVpreF or placebo. Maternal safety endpoints included local reactions/systemic events within 7 days, adverse events (AEs) through 1 month, and serious AEs (SAEs) through 6 months after vaccination. In infants born to maternal participants, safety endpoints included specific birth outcomes, AEs through 1 month after birth, and SAEs and newly diagnosed chronic medical conditions through 12 or 24 months after birth. Vaccine efficacy in infants was assessed against RSV-positive, medically attended LRTI (RSV-MA-LRTI) and severe RSV-MA-LRTI through 180 days after birth. RESULTS: In Japan, 230 maternal participants received RSVpreF and 232 received placebo; 218 and 216 infants born to these mothers, respectively, were analyzed. Observed vaccine efficacy (95 % CIs) against infant RSV-MA-LRTI within 90 and 180 days after birth was 100.0 % (30.9, 100.0; RSVpreF, 0 cases; placebo, 7 cases) and 87.6 % (7.2, 99.7; RSVpreF, 1 case; placebo, 8 cases), respectively. Vaccine efficacy (95 % CIs) against severe RSV-MA-LRTI within 90 and 180 days was 100.0 % (-140.9, 100.0; RSVpreF, 0 cases; placebo, 3 cases) and 75.1 % (-151.5, 99.5; RSVpreF, 1 case; placebo, 4 cases), respectively. No safety concerns were identified. AE rates ≤1 month after vaccination/birth were similar in the RSVpreF (maternal, 16.1 %; infant, 48.6 %) and placebo (19.8 %; 50.5 %) groups. Preterm birth rates were also similar (RSVpreF, 3.2 %; placebo, 6.0 %). CONCLUSIONS: Safety and efficacy data in Japanese participants were consistent with overall MATISSE results, supporting the efficacy of maternal RSVpreF vaccination against severe MA-RSV-LRTI/MA-RSV-LRTI in infants, with no safety concerns. NCT04424316.

Diagnosis, clinicopathologic features, treatment, and prognosis of small cell carcinoma of the uterine cervix; Kansai Clinical Oncology Group/Intergroup study in Japan.

OBJECTIVES: This is a multicenter, collaborative study to accumulate cases of small cell carcinoma of the uterine cervix (SmCC), to clarify its clinical and clinicopathologic features and prognosis, and to obtain findings to establish future individualized treatment. METHODS: At medical centers participating in the Kansai Clinical Oncology Group/Intergroup, patients diagnosed with SmCC between 1997 and 2007 were enrolled. Clinicopathologic features and prognosis were retrospectively evaluated in patients with SmCC diagnosed at a central pathologic review. RESULTS: A total of 71 patients were registered at 25 medical centers in Japan. Of these, 52 patients (73%) were diagnosed with SmCC based on a pathological review. These 52 patients diagnosed with SmCC were analyzed. The median follow-up period was 57 months. The 4-year progression-free survival (PFS) was: IB1, 59%; IB2, 68%; IIB, 13%; and IIIB, 17%. The 4-year overall survival (OS) was: IB1, 63%; IB2, 67%; IIB, 30%; IIIB, 29%; and IVB, 25%. For postoperative adjuvant therapy, postoperative chemotherapy (a platinum drug in all cases) was compared to non-chemotherapy. The 4-year PFS was 65% and 14%, and the 4-year OS was 65% and 29%. PFS was significantly better (p=0.002), and the OS tended to be better (p=0.073) in the group with postoperative chemotherapy. CONCLUSION: Even in patients with early stage SmCC, the prognosis is poor. However, in early stage patients, by adding postoperative chemotherapy, the prognosis may improve. Currently, various treatment protocols are used at each medical center, but in the future, a standardized treatment protocol for SmCC will hopefully be established.

Clinicopathologic features of brain metastases from gynecologic malignancies: a retrospective study of 139 cases (KCOG-G1001s trial).

OBJECTIVE: Although brain metastases from gynecologic malignancies are rare, such cases have been gradually increasing in number. The aim of the present study was to evaluate the clinicopathologic features and prognostic factors of brain metastases from gynecologic malignancies. METHODS: Retrospective analysis of 139 patients with brain metastases from gynecologic malignancies was carried out as a multi-institutional study. The clinicophathological data of the patients were collected from medical records. RESULTS: Median survival time of the patients with brain metastases was 12.5 months for the ovarian cancer group, 6.2 months for the corpus cancer group, and 5.0 months for the cervical cancer group; two-year overall survival rates were 19.7%, 6.1%, and 4.8%, respectively. Multivariate analysis revealed ovarian/tubal/peritoneal origin, KPS >70, single brain metastasis, absence of extracranial disease, cranial surgery, cranial radiotherapy, and chemotherapy to be independent favorable prognostic factors associated with overall survival. CONCLUSION: It is considered that aggressive multimodal therapy is warranted in the treatment of brain metastases from gynecologic malignancies in carefully selected patients. The present study may provide a platform for the discussion of management strategies in these rare clinical scenarios.

Applicability of the concept of "platinum sensitivity" to recurrent endometrial cancer: the SGSG-012/GOTIC-004/Intergroup study.

OBJECTIVE: The concept of "platinum sensitivity" has been widely applied in the management of recurrent ovarian cancer. This study aimed to evaluate the applicability of this concept to recurrent endometrial cancer. PATIENTS AND METHODS: In this multicenter retrospective cohort study, the clinical data of patients with recurrent endometrial cancer, who had a history of receiving first-line platinum-based chemotherapy and who received second-line platinum-based chemotherapy at the time of recurrence between January 2005 and December 2009 were reviewed. RESULTS: A total of 262 patients from 30 centers with initial FIGO stage classifications of I (29), II (23), III (122), and IV (88) were enrolled. In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear cell adenocarcinomas, 36 carcinosarcomas, and 22 "other" tumors were documented. The response rates for patients with platinum-free intervals of <6 months, 6-11 months, 12-23 months, and ≥24 months were 25%, 38%, 61%, and 65%, respectively. The median progression-free survival after second-line platinum-based chemotherapy for patients with platinum-free intervals of <12 months and ≥12 months was 4.4 (95% confidence interval (CI)=3.7-5.8) months and 10.3 (95% CI=8.2-12.6) months, respectively (log-rank P<0.0001), and the median overall survival was 13.8 (95% CI=10.6-18.1) months and 40.9 (95% CI=25.3-54.2) months, respectively (log-rank P<0.0001). CONCLUSION: Platinum-free interval is a predictor of response and survival after second-line platinum-based chemotherapy in patients with recurrent endometrial cancer. The concept of "platinum sensitivity" could be applicable to recurrent endometrial cancer.

Detection of sentinel lymph node metastases in cervical cancer: assessment of KRT19 mRNA in the one-step nucleic acid amplification (OSNA) method.

OBJECTIVE: The purpose of this study was to examine the utility of the one-step nucleic acid amplification (OSNA) assay using cytokeratin (CK) 19 (KRT19) messenger RNA (mRNA) for the detection of sentinel lymph node (SLN) metastases in cervical cancer patients. METHODS: To determine a cutoff value, KRT19 mRNA was assessed by OSNA assay using 239 lymph nodes (LNs) (217 histopathologically negative LNs and 22 positive LNs). A cutoff value was determined by statistical analysis of the copy numbers obtained by OSNA assay. Subsequently, performance evaluation of the OSNA assay (applying the cutoff value above) on 130 SLNs (32 patients) was used to investigate (through concordance) whether the OSNA assay exhibited diagnostic performance equivalent to the two-mm interval histopathological examination. RESULTS: Two hundred fifty copies/µL of KRT19 mRNA in the OSNA assay appeared to be an optimal cutoff value. In performance evaluation of the OSNA assay, we identified five positive SLNs and 125 negative SLNs by OSNA assay using KRT19 mRNA, exhibiting 96.2% agreement with two-mm interval histopathological examination. CONCLUSIONS: Our results indicated that the KRT19 mRNA OSNA assay can detect LN metastases as accurately as two-mm interval histopathological examination and thus may be an effective additional or alternative method for a rapid intra-operative examination of SLNs in cervical cancer.

Small cell carcinoma of the uterine cervix: clinical outcome of concurrent chemoradiotherapy with a multidrug regimen.

Small cell carcinoma of the uterine cervix (SCCC) is a rare subtype of cervical cancer with an aggressive behavior. Although SCCC has a worse prognosis than other histological types of uterine cervical cancer such as squamous cell carcinoma or adenocarcinoma, standard therapy for SCCC remains to be established due to its rarity. The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) using a regimen consisting of vincristine, adriamycin, and cyclophosphamide alternating with cisplatin and etoposide (VAC/PE). We analyzed a series of 9 patients with SCCC. Five patients with stage IB disease underwent radical hysterectomy followed by CCRT. Four patients with advanced stage disease received CCRT primarily. With a median follow-up duration of 47.4 months (range, 10.5 to 86.4 months), 4 out of 5 patients with stage IB disease were alive without recurrence. In 4 patients with advanced stage disease, the response rate was 75% (complete response, 1; partial response, 2; progressive disease, 1). One patient with stage IVB disease remained without recurrence for 89.5 months. At 5 years, overall survival (OS) and progression-free survival for all patients was 52% and 56%, respectively. Patients with early-stage disease had an 80% 5-year OS rate compared to 25% for patients with advanced stage disease. Although all patients developed grade 3-4 neutropenia, CCRT using VAC/PE is feasible in both the primary and adjuvant settings for SCCC. In particular, this combined modality therapy may improve both local control and survival as postoperative treatment in patients with early-stage disease.

Decreased expression of 14-3-3σ is predictive of poor prognosis for patients with human uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ-positive UPSC and 80% of 14-3-3σ-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC.

Prospective study of sentinel lymph node biopsy without further pelvic lymphadenectomy in patients with sentinel lymph node-negative cervical cancer.

OBJECTIVE: The aim of the present study was to evaluate the incidence of lymphedema and cancer recurrence rate in patients with cervical cancer who undergo sentinel lymph node (SLN) biopsy alone in the absence of SLN metastases. PATIENTS AND METHODS: The study included 35 consecutive patients with cervical cancer scheduled for radical hysterectomy at Tohoku University Hospital between May 2006 and July 2009. All patients had International Federation of Gynecology and Obstetrics stages IA1 to IIA1 disease. Patients in whom SLNs were detected unilaterally or not detected and/or whose lymph nodes were diagnosed intraoperatively as positive metastasis underwent systemic pelvic lymphadenectomy. Patients who were found negative for SLN metastasis did not undergo further pelvic lymphadenectomy. RESULTS: The mean number of detected SLNs was 4.1 (range, 1-11). True lymph node metastasis could be detected in 11 (31%) of the 35 cases. Intraoperative frozen section identified correctly in 8 of 11 metastatic patients. Twenty-three patients underwent SLN biopsy alone without systematic pelvic lymphadenectomy. None of the 23 patients diagnosed with negative SLNs have experienced a lymph node recurrence in the pelvic cavity. New symptomatic lower extremity lymphedema was identified in 2 (8.7%) of the 23 patients who underwent SLN biopsy alone and in 5 (42%) of 12 patients who underwent systematic lymphadenectomy. CONCLUSION: Radical hysterectomy with SLN biopsy alone seems to be a safe and effective strategy for detection of lymph node metastasis and for reducing the number of patients with lower extremity lymphedema, but a more convenient and sensitive procedure for intraoperative diagnosis needs to be established.

Individualized radical hysterectomy procedure using intraoperative electrical stimulation for patients with cervical cancer.

OBJECTIVE: In this study, by monitoring the varied distributions of nerve fascicles using intraoperative electrical stimulation (IES), we sought to establish an individualized operation based on the patient's unique nerve distribution pattern, and to determine whether this technique would result in a higher preservation rate. MATERIALS/METHODS: Radical hysterectomy was performed from 2002 to 2010. Patients in group A are the 48 cases from 2002 to 2007 in which nerve-sparing radical hysterectomy using IES as our previous report was performed. Patients in group B are the 38 cases from 2008 to 2010 in which we used our new method, which was individualized to each patient. Urodynamic study (UDS) was used to confirm nerve preservation. Nerve preservation was defined as confirming distinct detrusor contraction during urinary voiding. RESULTS: In group B, nerve preservation rate was higher than in group A (75% vs 9 0%, P = 0.067). We classified the case-by-case nerve anatomy as whether the nerve fascicle was mainly on the medial side or on the lateral side of the deep uterine vein. The lateral type anatomy was observed unilaterally in 6 cases and bilaterally in 1 case. In summary, the lateral type anatomy was observed in 8 (29%) of 28 sides. In the cases evaluated by UDS, the positive predictive value of IES was 95% in group A and 100% in group B. CONCLUSIONS: Our method of IES showed a high positive predictive value of nerve preservation as confirmed by UDS. By delineating the nerve tract in detail using IES, it is possible to individualize the operation based on each patient's anatomy, with an improved nerve preservation rate.

Hysteroscopic inspection and total curettage are insufficient for discriminating endometrial cancer from atypical endometrial hyperplasia.

Endometrial cancer (EC) is the most prevalent gynecologic malignancy in Japan. Atypical endometrial hyperplasia (AEH) is viewed as the premalignant lesion of EC, however it is often difficult to distinguish EC from AEH. The rate of concurrent EC in women diagnosed preoperatively with AEH based on endometrial biopsy was reported as 17-52%. Although hysteroscopic inspection and total curettage are considered as useful methods to make diagnosis of endometrial lesions, there is no report using this combined method to discriminate EC from AEH. The purpose of this study was to examine whether hysteroscopic inspection and total curettage improve the prevalence of EC among women diagnosed preoperatively with AEH. We reviewed 22 patients who underwent hysteroscopic inspection and total curettage and were diagnosed with AEH before undergoing hysterectomy between November 2001 and May 2011. The diagnosis made with the hysterectomy specimens revealed AEH in 10 patients (45.5%), endometrial hyperplasia without atypia in 3 (13.6%), and endometrioid adenocarcinoma, the most common type of EC, in 9 (40.9%). Endometrioid adenocarcinoma included 7 patients without myometrial invasion (31.8%) and 2 patients with superficial myometrial invasion (9.1%). There was no hysteroscopic finding that was specific for EC or AEH. In conclusion, about 41% of women who underwent hysterectomy under a diagnosis of AEH were found to have coexisting adenocarcinoma, although the prevalence of EC among those women was similar to that in earlier reports with endometrial biopsy. Accordingly, we must be careful in planning the therapeutic strategy for women with a preoperative diagnosis of AEH.

Brachial Artery Dissection Caused by Closed Elbow Dislocation in a Snowboarder: A Case Report and Review of Literature.

This report describes a rare case of brachial artery dissection associated with closed elbow dislocation caused by a snowboarding injury. After peripheral ischaemic findings in the right upper extremity were confirmed, urgent duplex-sonography was performed to diagnose the brachial artery injury. Urgent revascularisation surgery was promptly performed, and arterial dissection was diagnosed by intraoperative findings, in which the adventitia of the brachial artery was intact and the intima was disrupted. In this case, because there was no golden time window before undertaking urgent revascularisation surgery, duplex-sonography was very useful for making an emergency diagnosis. To diagnose arterial dissection, because the adventitia of the brachial artery is intact, it is necessary to perform arteriotomy to identify intimal disruption in the brachial artery. When diagnosing traumatic elbow dislocation, it is important to suspect arterial dissection.

Malignant transformation arising from mature cystic teratoma of the ovary: a retrospective study of 20 cases.

OBJECTIVES: Mature cystic teratoma (MCT) of the ovary rarely undergoes malignant transformation (MT). Malignant transformation carries a significantly worse prognosis than epithelial ovarian cancer, regardless of whether postoperative chemotherapy or radiotherapy is applied. The rarity of this tumor has posed a significant challenge to developing standardized postoperative management protocols. The aim of this study was to review our experience with MT and to describe our current treatment practices. METHODS: A retrospective chart review of these patients was performed that identified 20 women treated for MT of MCT at our centers between 1988 and 2008. RESULTS: The median age was 52.5 (range, 29-77) years. Fifteen patients had squamous cell carcinoma (SCC), and 5 patients had other histological subtypes. The International Federation of Gynecology and Obstetrics stage distribution was as follows: 11 were stage I, 4 were stage II, 4 were stage III, and 1 was stage IV. All patients underwent an initial laparotomy. Eleven patients received adjuvant treatment: 8 were treated with chemotherapy, 2 with concurrent chemoradiation therapy, and 1 with radiation therapy. Platinum-based chemotherapy was the first-line regimen. The overall 1-year survival rate was 70%. Significant correlations between overall survival and age, stage, and residual tumor were presented (P = 0.044, P = 0.0107, P < 0.0001, respectively). Eight patients with advanced stage died of their disease. Four patients, however, were treated with adjuvant chemotherapy or concurrent chemoradiation therapy and survived more than 1 year. One stage III patient had a disease-free interval of 2 years. Two cases of SCC treated with combination platinum/taxane chemotherapy temporarily responded. In the other 2 cases of SCC, concurrent chemoradiation therapy with nedaplatin also resulted in tumor regression. CONCLUSIONS: The prognosis of MT is highly dependent on age, stage, and optimal cytoreduction. Adjuvant treatment has not been standardized, although our experience supports the use of combination platinum/taxane chemotherapy.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.