[Reducing the Time Before the Console in Robotic-Assisted Laparoscopic Hysterectomy].

Robotic-assisted surgery enables precise manipulations with magnified vision, stereoscopic vision, and forceps with multi-joint functions. It requires unique procedures such as position setting, port placement, roll-in, and docking, which lead to prolonged operation and anesthesia time. Five conditions described below were established at our institution to reduce the time to the initiation of console: (1) changing the patients' position from the flat lithotomy position to the spread legs position; (2) attaching a Hasson cone to hold the umbilical cannula stable; (3) changing the cannula's obturator (inner tube) from blunt to bladeless; (4) fixing the team, and (5) conducting regular docking training. These outcomes were examined in this study. The study included 77 patients who underwent robotic-assisted total hysterectomy for benign uterine disease and stage IA uterine cancer at our individual institution between April 2019 and July 2022. We compared the median time from anesthesia to console initiation between the first half group (cases 1-40) and the second half group (cases 41-77). The former required 91.5 (53-131) minutes, whereas the latter required 59 (37-126) minutes. Appropriate equipment selection and team education can reduce the time to console initiation.

[A Case of Adenocarcinoma, HPV-independent, Mesonephric Type with Significant Response to Neoadjuvant Chemotherapy].

Adenocarcinoma, HPV-independent, mesonephric type (hereafter referred to as "mesonephric carcinoma") arising from the cervix is rare, its treatment has not been established, and its sensitivity to chemotherapy has not been fully investigated. Here we report on a 30-year-old female patient who presented at our hospital with a chief complaint of abnormal genital bleeding. We suspected cervical cancer. Based on examination, biopsy, and imaging, she was diagnosed with stage IIA2 adenocarcinoma of the cervix and was scheduled for surgery. Because she had a SARS-COV-2 infection, she was given two courses of paclitaxel-carboplatin (TC) therapy, based on the then-current surgical risk assessment after SARS-COV-2 infection, with a waiting period of at least 8 weeks. The patient was deemed to have a partial response and was treated with paclitaxel and carboplatin, after which she was deemed to have a partial response and underwent total hysterectomy. A diagnosis of stage IIA2 mesonephric carcinoma, ypT1b2N0M0, was made after histopathologic examination of an excised specimen. The patient was treated with 4 additional courses of TC therapy after surgery, and has had no recurrence in 13 months. We report a first case of response to neoadjuvant chemotherapy with TC regimen in a patient with mesonephric carcinoma of the cervix.

Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2020 and Annual Treatment Report for 2015.

AIM: To provide information including the trend of gynecological malignancies in Japan, we hereby present the annual patient report for 2020 and the Annual Treatment Report for 2015, on the outcomes of patients who started treatment in 2015. METHODS: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2020 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2015 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. RESULTS: Treatment was initiated in 2020 for 7689 patients with cervical cancer, 13 113 with endometrial cancer, 8004 with ovarian, tubal, and peritoneal cancer, 2152 with ovarian borderline tumors, and with the others (260 vulvar cancer, 157 vaginal cancer, 464 uterine sarcoma, 50 uterine adenosarcoma, 136 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.3%, 76.2%, 56.5%, and 32.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.9%, 87.6%, 71.4%, and 29.3% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 91.7%, 80.6%, 50.8%, and 39.7% for Stages I, II, III, and IV, respectively. CONCLUSION: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Ovarian Clear Cell Carcinoma and Rectal Adenocarcinoma Detected by Tubo-Ovarian Abscess: A Case Report.

Most cases of tubo-ovarian abscess (TOA) are due to transvaginal infection, while other internal diseases may also be associated with TOAs. We experienced a case of ovarian clear cell carcinoma and rectal carcinoma that was discovered to be a result of TOA. A 46-year-old woman was diagnosed with TOA and referred to our hospital. Laparoscopic abscess drainage was performed, and pathological findings confirmed the presence of ovarian clear cell carcinoma inside the abscess. The tumor marker carcinoembryonic antigen (CEA) was elevated, and rectal cancer was diagnosed by a gastrointestinal endoscopy. Abdominal computed tomography (CT) showed a left adnexal abscess with an air image inside, and penetration of the abscess wall and rectal cancer were observed. Histopathologically, there was an accumulation of neutrophils around the rectal tumor cells. We concluded that the rectal cancer had penetrated the existing ovarian tumor and formed TOA. Non-gynecological diseases may be associated with TOA. It is necessary to consider the possibility that other clinical diseases may be associated with the trigger of TOA.

Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2019 and annual treatment report for 2014.

AIM: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2019 and the Annual Treatment Report for 2014, on the outcomes of patients who started treatment in 2014. METHODS: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2019 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2014 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. RESULTS: Treatment was initiated in 2019 for 7983 patients with cervical cancer, 12 631 with endometrial cancer, 7737 with ovarian, tubal, and peritoneal cancer, 2222 with ovarian borderline tumors, and with the others (251 vulvar cancer, 148 vaginal cancer, 476 uterine sarcoma, 43 uterine adenosarcoma, 175 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 92.5%, 76.8%, 58.6%, and 29.5% for stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.5%, 87.3%, 70.2%, and 26.5% for stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 90.72%, 80.4%, 53.4%, and 31.6% for stages I, II, III, and IV, respectively. CONCLUSION: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

Poorly Differentiated Cervical Squamous Cell Carcinoma Resembling Giant Cell Carcinoma of the Lung: Extreme Morphology of This Tumor and Its Clinical Course.

Giant cell tumor is a highly aggressive tumor characterized by a marked proliferation of pleomorphic, bizarre giant cells usually observed in the lungs. The importance of histopathological imaging and the clinical course of this tumor are unknown. The objective of our report was to investigate whether these components affect treatment outcomes and prognosis compared to conventional cancers. A 40-year-old woman with cervical cancer showed leukocytosis and elevated granulocyte colony simulating factor (G-CSF). The patient underwent a radical abdominal hysterectomy. Pathology revealed a poorly differentiated squamous cell carcinoma of the cervix, similar to giant cell carcinoma. The patient recovered from the disease and is alive 37 months after concurrent chemoradiotherapy (CCRT). Leukocytosis and G-CSF were normalized after treatment. This was our second case of giant cell carcinoma of the cervix. Cumulative data on giant cell carcinoma are limited, thus we considered the prognostic significance of the presence of giant cell carcinoma in uterine carcinoma.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Laparoscopic pelvic exenteration and laterally extended endopelvic resection for postradiation recurrent cervical carcinoma: Technical feasibility and short-term oncologic outcome.

OBJECTIVE: Surgery is the only treatment for cervical cancer recurrence in a previously irradiated field. Pelvic exenteration (PE) and laterally extended endopelvic resection (LEER) are indicated for select patients; however, morbidity and mortality rates remain high, and new treatment modalities are required. Laparoscopy optimizes visualization and allows meticulous dissection while also reducing intraoperative blood loss and postoperative complications without worsening the outcomes. We aimed to clarify the feasibility and outcomes of laparoscopic PE and LEER for previously irradiated recurrent cervical cancer. METHODS: We prospectively investigated the outcomes of laparoscopic PE and LEER in 28 patients with recurrent cervical carcinoma after radiotherapy. RESULTS: Seventeen laparoscopic PEs for central recurrences and 11 laparoscopic LEERs for lateral recurrences were performed. The median operation time and blood loss were 454mins and 285 mL in the PE group, and 562mins and 325 mL in the LEER group, respectively, with no conversions to laparotomy. R0 resection was achieved in all patients in the PE group and 73% in the LEER group. The morbidity and mortality rates were 41% and 0% in PE group, and 55% and 0% in LEER group, respectively. The 2-year disease-free survival and overall survival were 68.9% and 76% in the PE group, and 27.3% and 29.6% in the LEER group, respectively. CONCLUSION: Laparoscopic PE is feasible for previously irradiated central recurrent cervical cancer and has acceptable outcomes. Laparoscopic LEER is also feasible for lateral recurrence, but oncologic outcome may be modest in this limited preliminary study. Further studies using a larger sample size with a longer follow-up period is warranted to determine the indications for laparoscopic LEER.

Positive surgical margin is an independent predictor of overall survival of patients with vulvar squamous cell carcinoma.

AIM: It is uncertain whether curative surgical treatment or a less radical surgery with adjuvant treatment should be provided to preserve function in patients with vulvar squamous cell carcinoma (SCC) that is adjacent to the urethra, anus, and vagina. The aim of this study was to investigate the surgical margin in patients with vulvar SCC with regard to local recurrence and overall survival. METHODS: Thirty-four patients were identified as having a diagnosis of vulvar SCC without distant metastasis. They had been treated surgically with curative intent at the Cancer Institute Hospital. Clinical data were analyzed retrospectively. RESULTS: Rates of 5-year local recurrence-free survival among patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 32%, 30.3%, 42.5%, 55.5%, and 73%, respectively. Rates of 5-year overall survival of patients with positive, <3-mm, <5-mm, <8-mm, and ≥8-mm surgical margins were 15.5%, 53.8%, 58.8%, 67.6%, and 83.3%, respectively. In the multivariable analysis, a tumor size of more than 2-cm (hazard ratio [HR] = 17.7, 95% confidence interval [CI] = 1.39-226) and a positive surgical margin (HR = 0.0092, 95% CI = 0.011-0.53) were risk factors for local recurrence, and a lymph node involvement (HR = 1.41, 95% CI = 0.31-6.43) and a positive surgical margin (HR = 0.0046, 95% CI = 0.011-0.53) were significant risk factors for overall mortality. CONCLUSIONS: To improve the prognosis, thorough resection with an adequate surgical margin is needed. But narrow surgical margin may be acceptable, particularly to preserve the function of adjacent organs.

Moving a neodymium magnet promotes the migration of a magnetic tracer and increases the monitoring counts on the skin surface of sentinel lymph nodes in breast cancer.

BACKGROUND: We suspected that moving a small neodymium magnet would promote migration of the magnetic tracer to the sentinel lymph node (SLN). Higher monitoring counts on the skin surface before making an incision help us detect SLNs easily and successfully. The present study evaluated the enhancement of the monitoring count on the skin surface in SLN detection based on the magnet movement in a sentinel lymph node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles. METHODS: After induction of general anesthesia, superparamagnetic iron oxide nanoparticles were injected sub-dermally into the subareolar area or peritumorally. The neodymium magnet was moved over the skin from the injection site to the axilla to promote migration of the magnetic tracer without massage. A total of 62 patients were enrolled from February 2018 to November 2018: 13 cases were subjected to magnet movement 20 times (Group A), 8 were subjected to 1-min magnet movement (Group B), 26 were given a short (about 5 min) interval from injection to 1-min magnet movement (Group C), and 15 were given a long (about 25 min) interval before 1-min magnet movement using the magnetometer's head (Group D). In all cases, an SNB was conducted using both the radioisotope (RI) and SPIO methods. The monitoring counts on the skin surface were measured by a handheld magnetometer and compared among the four groups. Changes in the monitoring count by the interval and magnet movement were evaluated. RESULTS: The identification rates of the SPIO and RI methods were 100 and 95.2%, respectively. The mean monitoring counts of Group A, B, C, and D were 2.39 µT, 2.73 µT, 3.15 µT, and 3.92 µT, respectively (p < 0.0001; Kruskal-Wallis test). The monitoring counts were higher with longer magnet movement and with the insertion of an interval. Although there were no relationships between the monitoring count on the skin surface and clinicopathologic factors, magnet movement strongly influenced the monitoring count on the skin surface. CONCLUSION: Moving a small neodymium magnet is effective for promoting migration of a magnetic tracer and increasing monitoring counts on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000029475. Registered 9 October 2017.

Surgical outcomes of early-stage primary vaginal nonsquamous cell carcinoma.

OBJECTIVE: Definitive radiation therapy (RT), using external beam RT and/or brachytherapy, is a standard treatment option for primary vaginal carcinoma. However, this treatment has poor prognosis when applied to vaginal nonsquamous cell carcinoma (non-SCC). We aimed to clarify treatment outcome and surgical safety in early-stage primary vaginal non-SCC. METHODS: After receiving approval from the institutional review board, we retrospectively reviewed the clinical records and pathological samples of patients treated at our hospital between 1991 and 2018. Among 49 patients with primary vaginal carcinoma, 12 with histologically confirmed early-stage primary vaginal non-SCC were included in this study. RESULTS: In total, 40% of patients with primary vaginal carcinoma treated at our hospital had primary vaginal non-SCC. The average observation time was 34 months (median 53.3 months). Three patients had local recurrence: 2 in pelvic lymph nodes and 1 in the vagina. Furthermore, 2 patients died of their disease. Five-year local control rate of stage I and stage II non-SCC was 75% and 100%, respectively. Disease-specific survival rate of stage I and stage II non-SCC was 81.8% and 100%, respectively. No major morbidity was observed. Three patients required allogeneic blood transfusion, whereas 1 underwent autotransfusion. None of the 12 patients were discharged with self-catheterization. CONCLUSION: Five-year local control and disease-specific survival rates of patients surgically treated for vaginal non-SCC were favorable. Therefore, surgery could be a safe and reasonable option for early-stage primary vaginal non-SCC.

Laparoscopically Resected Venous Adventitial Cystic Disease that was Difficult to Distinguish from an Ovarian Tumor.

Adventitial cystic disease (ACD) is a rare condition in which a mucinous cyst forms within the adventitia, usually in arteries but rarely in veins. A 79-year-old patient presented with stomachache and nausea. Computerized tomography showed pelvic cysts on either side of the pelvis. The right tumor was 120×100 mm, and the left tumor was 45×35 mm. Our diagnosis was bilateral ovarian tumors and we performed laparoscopic tumor resection. In the abdominal cavity, we saw that the left ovary was swollen by about 3-4 cm and the right ovary was normal size. There was a mucous cyst located in the right retroperitoneal cavity that adhered around and bordered the right external iliac vein and the right obturator nerve. We peeled the adhesion away carefully and resected the tumor but the operation caused temporary obturator nerve paralysis. From pathological examination, we diagnosed the right retroperitoneal cyst to be venous ACD originating from the right external iliac vein. We found that venous ACD can grow as large as a pelvic tumor and is difficult to distinguish from an ovarian tumor, which is why we chose laparoscopic surgery. In this case, we performed the operation laparoscopically and no sequelae or recurrent tumor appeared during a 1-year follow-up. However, graft replacement is sometimes necessary for ACD, thus venous ACD should be considered a differential diagnosis and a surgical strategy should be developed when pelvic tumors are observed.

Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

BACKGROUND: Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node-negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection. METHODS: Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids (99m Tc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan. RESULTS: Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%. CONCLUSION: This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.

Immunohistochemical Analysis of the Effect of Dienogest on Ovarian Endometriotic Cysts.

Dienogest is a novel progestin with potent oral progestational activity that inhibits the clinical symptoms of endometriosis. We herein evaluated the effect of dienogest on ovarian endometriotic cysts via immunohistochemistry. Ovarian endometriotic cyst specimens were collected from 12 patients treated with dienogest and 20 patients not treated with hormones (controls). The expression of estrogen receptor (ER)-α, progesterone receptor A (PRA), and Ki-67 was studied by immunohistochemistry. As compared with the controls, the cell proliferation index was significantly reduced in both epithelial and stromal cells of the endometriotic cysts following the use of dienogest (P = 0.022 and P = 0.004, respectively). However, there was no significant difference between endometriotic cysts with and without the use of dienogest in the expressions of ER-α and PRA in the epithelial and stromal cells. Irrespective of the use of dienogest, the expression levels of ER-α and PRA in the epithelial cells were low (median: 32% and 8%, respectively). Conversely, the expression levels of ER-α and PRA in the stromal cells were well preserved (median: 68% and 92%, respectively). In the controls, there was no significant difference between endometriotic cysts in the expression levels of Ki-67, ER-α and PRA in epithelial and stromal cells during the proliferative and secretory phases. The finding of a reduction in the cell proliferation index by the use of dienogest with no change in the expressions of hormonal receptors may not support the direct progestational effect of dienogest on ovarian endometriotic cysts.

Expression of BAF57 in ovarian cancer cells and drug sensitivity.

The SMARCE1 (SWI / SNF-related, matrix-associated, and actin-dependent regulator of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we reported that BAF57 is a predictive marker of endometrial carcinoma. In this study, we investigated BAF57 expression in ovarian cancer cell lines and their sensitivities to cisplatin, doxorubicin, paclitaxel, and 5-fluorouracil. BAF57 expression was strongly correlated with sensitivities to cisplatin, doxorubicin, and 5-fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was also correlated with BAF57 expression, but without significance. In A2780 ovarian cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest at G1 phase and the sensitivities to these anticancer agents. cDNA microarray analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were positively regulated by BAF57, including ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer cells by Western blot analysis, and that ABCG2 gene expression might be regulated transcriptionally. These results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy.

The Relationship between Positive Peritoneal Cytology and the Prognosis of Patients with Uterine Cervical Cancer.

OBJECTIVE: We investigated the association of positive peritoneal cytology with prognosis in uterine cervical cancer. STUDY DESIGN: We reviewed the medical records and cytologic materials of 225 Japanese patients with FIGO IB1-IVB uterine cervical cancer who had undergone surgery at our University Hospital between 1993 and 2012. Univariate and multivariate regression analyses were performed for statistical analysis. RESULTS: Positive peritoneal cytology was noted in 6 of 225 patients (2.7%). Positive peritoneal cytology was found in 4 of 149 patients (2.6%) with squamous cell carcinoma (SCC) and in 2 of 70 patients (2.8%) with non-SCC (p = 0.9434). The 5-year survival rate of patients with positive peritoneal cytology was significantly lower than that of patients with negative cytology (50 vs. 84.6%, p = 0.001) in univariate survival analysis. However, peritoneal cytology no longer remained significant in multivariate analysis. CONCLUSION: Although we conclude that positive peritoneal cytology in uterine cervical cancer is a poor prognostic factor, further investigation and multi-institutional studies are necessary.

Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

Safety analysis of Epzicom® (lamivudine/abacavir sulfate) in post-marketing surveillance in Japan.

PURPOSE: To obtain safety and effectiveness data on a combined anti-HIV drug, Epzicom (abacavir 600 mg/lamivudine 300 mg), a post-marketing surveillance on Epzicom that was required by the Japanese regulatory authority was conducted between January 2005 and December 2010. METHODS: A joint survey (HIV-related drug [HRD] survey) has been conducted involving manufacturers of drugs for treatment of HIV infection in Japan. Safety and effectiveness data from total 624 cases (1107.3 person-years) registered to the HRD surveys and received Epzicom were obtained. Adverse drug reactions (ADRs) were defined as adverse events (AE) of which association with Epzicom could not be 'ruled out'. RESULTS: It was found that the incidence of ADR was 32.4% (202/624 cases) on the case basis. In addition, the frequently reported ADR included hyperlipidaemia (59 cases), hypertriglyceridaemia (21 cases), blood bilirubin increased (19 cases), gamma-glutamyltransferase increase (14 cases), blood triglyceride increase (14 cases) and rash (14 cases). Serious AEs were seen in 19 patients (30 events), including one death (no evident association with Epzicom). There were four cases (0.6%) of survey-defined 'hypersensitivity', and the incidence was 0.9% (4/445) among abacavir naïve patients; none of which was reported as serious. No case of myocardial infarction was reported. One pregnant case who delivered a normal baby by caesarean section was reported to have experienced aggravation of anaemia and nausea. CONCLUSIONS: The post-marketing surveillance indicated that the incidence of both ischaemic heart disease and hypersensitivity associated with Epzicom was considerably low, suggesting that this drug can be safely used in the Japanese population.

Safety analysis of Ziagen® (abacavir sulfate) in postmarketing surveillance in Japan.

PURPOSE: Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, Ziagen® (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009. METHODS: A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7 person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be "ruled out." RESULTS: It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were "hyperlipidemia," "nausea," "increased γ-glutamyltransferase level," "increased blood triglycerides," "abnormal hepatic function," and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion). CONCLUSIONS: During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance.