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Sota Tanaka,
Satoru Nagase,
Michiko Kaiho-Sakuma,
Tomoyuki Nagai,
Hiroki Kurosawa, Masafumi Toyoshima,
Hideki Tokunaga,
Takeo Otsuki,
Hiroki Utsunomiya,
Tadao Takano,
Hitoshi Niikura,
Kiyoshi Ito,
Nobuo Yaegashi
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ABSTRACT: 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.
International Journal of Clinical Oncology 02/2013; · 1.41 Impact Factor
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Hideki Tokunaga,
Satoru Nagase,
Kosuke Yoshinaga,
Sota Tanaka,
Tomoyuki Nagai,
Hiroki Kurosawa,
Michiko Kaiho-Sakuma, Masafumi Toyoshima,
Takeo Otsuki,
Hiroki Utsunomiya,
Tadao Takano,
Hitoshi Niikura,
Kiyoshi Ito,
Nobuo Yaegashi
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ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2013; 229(1):75-81. · 1.24 Impact Factor
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Hiroki Kurosawa,
Kiyoshi Ito,
Hitoshi Nikura,
Tadao Takano,
Satoru Nagase,
Hiroki Utsunomiya,
Takeo Otsuki, Masafumi Toyoshima,
Tomoyuki Nagai,
Souta Tanaka,
Mika Watanabe,
Nobuo Yaegashi
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ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2012; 228(4):365-70. · 1.24 Impact Factor
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ABSTRACT: In order to facilitate the discovery and investigation of anti-cancer therapeutics under physiological conditions, we have engineered the ovarian cancer cell line, HM-1/luc, in mice. This cell stably expresses firefly luciferase and produces light that can be detected using an in vivo imaging system (IVIS). Parental HM-1 cells cause severe carcinomatous peritonitis to B6C3F1 mice, but not to C57BL6 mice. Established HM-1/luc cells showed pathologically similar findings to HM-1 cells. HM-1/luc cells were injected into the peritoneal cavity of B6C3F1 mice and IVIS 2000 was conducted weekly after inoculation to monitor intra-peritoneal tumor growth. The mice were divided into three groups: non-CDDP-treated (control) and CDDP-treated (0.2 and 0.4 mg). A disease-suppressive effect of the CDDP was reflected by the significantly prolonged survival of the CDDP-treated mice (control 23 +/- 1.9 days, CDDP 0.2 mg 29.6 +/- 2.9 days; p < 0.05); the total photon and area of flux were decreased. The optical imaging of intraperitoneal tumors via in vivo bioluminescence is effective for noninvasive monitoring and semi-quantitative analysis. Our syngeneic mouse model has the relevant clinical features of ovarian cancer, which makes it a useful model for developing new ovarian cancer therapies.
Luminescence 09/2009; 24(5):324-31. · 1.73 Impact Factor
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Keiichi Tamai, Masafumi Toyoshima,
Nobuyuki Tanaka,
Noriko Yamamoto,
Yuji Owada,
Hiroshi Kiyonari,
Kazuko Murata,
Yoshiyuki Ueno,
Masao Ono,
Tooru Shimosegawa,
Nobuo Yaegashi,
Masahiko Watanabe,
Kazuo Sugamura
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ABSTRACT: The endosomal sorting complex required for transport (ESCRT) proteins form multimolecular complexes that control multivesicular body formation, endosomal sorting, and transport ubiquitinated membrane proteins (including cell-surface receptors) to the endosomes for degradation. There is accumulating evidence that endosomal dysfunction is linked to neural cell degeneration in vitro, but little is known about the relationship between neural disorders and ESCRT proteins in vivo. Here we specifically deleted the hrs gene, ESCRT-0, in the neurons of mice by crossing loxP-flanked hrs mice with transgenic mice expressing the synapsin-I Cre protein (SynI-cre). Histological analyses revealed that both apoptosis and a loss of hippocampal CA3 pyramidal neurons occurred in the hrs(flox/flox);SynI-cre mice. Notably, the hrs(flox/flox);SynI-cre mice accumulated ubiquitinated proteins, such as glutamate receptors and an autophagy-regulating protein, p62. These molecules are particularly prominent in the hippocampal CA3 neurons and cerebral cortex with advancing age. Accordingly, we found that both locomotor activity and learning ability were severely reduced in the hrs(flox/flox);SynI-cre mice. These data suggest that Hrs plays an important role in neural cell survival in vivo and provide an animal model for neurodegenerative diseases that are known to be commonly affected by the generation of proteinaceous aggregates.
American Journal Of Pathology 01/2009; 173(6):1806-17. · 4.89 Impact Factor
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Hitoshi Niikura,
Atsuko Katahira,
Hiroki Utsunomiya,
Tadao Takano,
Kiyoshi Ito,
Satoru Nagase,
Kohsuke Yoshinaga,
Hideki Tokunaga, Masafumi Toyoshima,
Yusuke Kinugasa,
Eiichi Uchiyama,
Gen Murakami,
Yoshihiko Yabuki,
Nobuo Yaegashi
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ABSTRACT: Radical hysterectomy has been performed for invasive cervical cancer, and autonomic nerve-sparing procedures have been developed to preserve bladder function. To perform and improve the nerve-sparing radical hysterectomy, it is important to understand anatomy of the intra pelvic fasciae, specially vesico-uterine ligament (VUL), because most of injuries to the nerves occurred during incision of the VUL in radical hysterectomy procedures. The objectives of the present study were to provide histological understanding of major structures found in nerve-sparing radical hysterectomy. Serial macroscopic slices (15-20 mm thick) from five female pelves were trimmed and prepared for paraffin-embedded histology. We noted an anatomical entity as "the visceroparietal fascial bridge", which corresponds with the macroscopically identified arcus tendineus fasciae pelvis. A histologically identifiable neurovascular pedicle to the bladder neck corresponded with the deep portion of VUL. These findings could help better preservation of autonomic nerves during radical hysterectomy and improve patient's quality of life after the operation. Translation of surgical anatomy into anatomic terminology enables us to have fruitful discussions with persuasive power by excluding any bias from individual surgeons.
The Tohoku Journal of Experimental Medicine 09/2007; 212(4):403-13. · 1.24 Impact Factor
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ABSTRACT: Abnormally high signals from receptor tyrosine kinases (RTK) are associated with carcinogenesis, and impaired deactivation of RTKs may also be a mechanism in cancer. Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is one of the master regulators that sort activated receptors toward lysosomes and shut down their signals. Hrs contains a ubiquitin-interacting motif and is involved in the endosomal sorting of monoubiquitinated membrane proteins, such as growth factor receptor and E-cadherin. Here, we investigated the role of Hrs in determining the malignancy of cancer cells and discovered that the targeted disruption of Hrs by small interfering RNA effectively attenuated the proliferation, anchorage-independent growth, tumorigenesis, and metastatic potential of HeLa cells in vitro and in vivo. The restoration of Hrs expression increased cell proliferation and anchorage-independent growth in a mouse embryonic fibroblast line established from a Hrs knockout mouse. Further analysis revealed that Hrs depletion was associated with the up-regulation of E-cadherin and reduced beta-catenin signaling. The aberrant accumulation of E-cadherin most likely resulted from impaired E-cadherin degradation in lysosomes. These results suggest that Hrs may play a critical role in determining the malignancy of cancer cells by regulating the degradation of E-cadherin.
Cancer Research 07/2007; 67(11):5162-71. · 7.86 Impact Factor
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Jun-ichi Akahira,
Hideki Tokunaga, Masafumi Toyoshima,
Tadao Takano,
Satoru Nagase,
Kosuke Yoshinaga,
Toru Tase,
Yuichi Wada,
Kiyoshi Ito,
Hitoshi Niikura,
Hidekazu Yamada,
Akira Sato,
Hironobu Sasano,
Nobuo Yaegashi
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ABSTRACT: The aims of this study were to evaluate the factors affecting prognosis in patients with uterine sarcomas and to demonstrate that carcinosarcoma bears a similarity to high-grade endometrial carcinoma in terms of its prognosis and clinicopathological parameters.
In June 2004, 17 Japanese institutions received questionnaires regarding uterine sarcomas. Study patients had uterine sarcomas initially treated at each institution between January 1990 and May 2004. Survival analyses and comparisons were performed by univariate methods. Patient data of 921 cases of endometrial adenocarcinoma were also analyzed and compared to the data with the uterine sarcomas.
One hundred twenty-one patients with uterine sarcomas were identified who met study eligibility criteria. In uterine sarcomas, carcinosarcoma had a worse prognosis than other sarcomas, but the difference was not significant (p = 0.302). In carcinosarcoma, significant differences were observed with age (p = 0.0388), stage (p < 0.01) and surgical procedure (with or without pelvic lymphadenectomy, p = 0.0316). In carcinosarcoma and G3 adenocarcinoma, no significant difference was identified with regard to overall survival in univariate (p = 0.191) and multivariate (p = 0.168) analyses.
Our results demonstrate that the clinical behavior of carcinosarcoma strongly resembles that of G3 endometrial adenocarcinoma, setting it apart from other 'pure' uterine sarcomas.
Oncology 01/2006; 71(5-6):333-40. · 2.27 Impact Factor
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ABSTRACT: Epithelioid leiomyosarcomas arising from the uterine cervix are extremely rare neoplasms, with only three cases reported in the English literature.
A 53-year-old Japanese woman was admitted to our university hospital due to massive vaginal bleeding from a cervical tumor. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Histological findings, including immunohistochemical study using desmin, SMA, cytokeratin, S-100, HMB-45, vimentin, melan-A, and CD68, led to a diagnosis of epithelioid leiomyosarcoma of the uterine cervix. The patient underwent adjuvant chemotherapy and has been disease-free for over 20 months.
Immunohistochemical studies may be needed to differentiate among the alternative diagnoses of malignant melanoma, metastatic carcinoma, and epithelioid sarcoma. Additional cases are needed to develop optimal management strategies and to predict prognosis.
Gynecologic Oncology 07/2005; 97(3):957-60. · 3.89 Impact Factor
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ABSTRACT: Primary vaginal adenosarcomas are extremely rare, and typical adenosarcomas are of low malignancy. However, aggressive forms with sarcomatous overgrowth have been reported, those appear to have a poor prognosis.
A 52-year-old woman who had undergone prior surgery for uterine leiomyoma and an ovarian cyst (total abdominal hysterectomy and left salpingo-oophorectomy) presented 10 years later with a rapidly enlarging tumor arising from the vaginal cuff. Repetitive biopsy samples revealed a mixture of benign epithelial gland and malignant stromal components with periglandular stromal hypercellularity and sarcomatous overgrowth. A histological diagnosis of mullerian adenocarcinoma was made. The patient died from recurrent disease 9 months after surgery.
Regardless of primary focus, adenosarcoma with sarcomatous overgrowth is associated with postoperative recurrence and a fatal outcome.
Gynecologic Oncology 01/2005; 95(3):759-61. · 3.89 Impact Factor
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ABSTRACT: The purpose of the study was to evaluate the efficacy of combination chemotherapy with paclitaxel and carboplatin in patients with advanced or recurrent carcinosarcoma of the uterus.
A retrospective review was carried out at Miyagi Prefecture Cancer Research Center Hospital. Six patients pathologically diagnosed with uterine carcinosarcoma were treated with paclitaxel (175 mg/m(2) given intravenously over 3 h) and carboplatin (dosed at AUC 6) every 3 weeks at our center between 1997 and 2003. Responses and adverse effects were assessed according to Response Evaluation Criteria in Solid Tumors and National Cancer Institute-Common Toxic Criteria, respectively.
All six patients were evaluable for toxicity, and no unacceptably severe toxicities were reported. Grades 3 and 4 hematologic toxicities occurred, but all of them were overcome by adequate treatment with granulocyte colony-stimulating factor and blood transfusions. Five of six patients had measurable disease and thus were evaluable for response: Four patients had a complete response (CR) and the remaining patient had progressive disease (PD). The median progression-free interval (PFI) for all six cases was 18 months, with a median overall survival of 25 months.
Although the number of cases was small, the regimen evaluated in the current study demonstrated higher activity and lesser toxicity than those found in previous studies in patients with advanced or recurrent uterine carcinosarcoma. Additional phase II clinical studies are necessary to evaluate fully the benefits of this regimen.
Gynecologic Oncology 10/2004; 94(3):774-8. · 3.89 Impact Factor
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ABSTRACT: To reduce the severity of post procedure pain associated with uterine artery embolization (UAE) for leiomyomata, we used continuous infusion of low concentration ropivacaine through an epidural catheter.
Thirteen patients for UAE were evaluated. In a patient without indication for epidural anesthesia, the pain was controlled with intermittent morphine infusion. Other patients had post procedure pain managed with 10 ml bolus of 1% lidocaine and continuous infusion of 0.2% ropivacaine at 5 ml x hr-1 for 16 hours.
The patient complained of severe pain just after UAE and required epidural lidocaine. Then, we started to infuse lidocaine or ropivacaine just before starting UAE. Among these cases, 9 patients required extra pain control using NSAIDs as a rescue. Only three patients required no medication except epidural analgesia.
Continuous infusion of 0.2% ropivacaine at a rate of 5 ml x hr-1 is not enough for pain management after UAE.
Masui. The Japanese journal of anesthesiology 05/2004; 53(4):391-5.
