Mamoru Kakuda

Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

OBJECTIVE: To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81–100 mg/d). METHODS: A multicenter retrospective study was conducted examining patients with stage I–IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. RESULTS: One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8–11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25–0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08–0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all P<.05). CONCLUSION: Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative radiotherapy.

A Case Report and Literature Review of Midtrimester Termination of Pregnancy Complicated by Placenta Previa and Placenta Accreta.

Objective Concurrent placenta previa and placenta accreta increase the risk of massive obstetric hemorrhage. Despite extensive research on the management of placenta previa (including placenta accreta, increta, and percreta), the number and quality of previous studies are limited. We present a case of placenta accreta requiring an induced second-trimester abortion because of premature rupture of the membranes (PROM). Study Design Case report and review of the literature. Results A 41-year-old female presented at 20 weeks of gestation with placenta previa and PROM. Ultrasonography revealed placenta accreta with multiple placental lacunae. She then developed massive hemorrhaging just prior to a planned termination of pregnancy. We performed a hysterectomy with the intent of preserving life because of the failure of the placenta to detach and blood loss totaling 4,500 mL. Conclusion Previous studies suggest that second-trimester pregnancy terminations in cases of placenta previa which are not complicated with placenta accreta do not have a particularly high risk of hemorrhage. However, together with our case, the literature suggests that placenta previa complicated with placenta accreta presents a significant risk of hemorrhage both during delivery and intraoperatively. Further reports are needed to evaluate the most appropriate treatment options.

Utility of an Internal Retractor (EndoGrab) for the Management of the Vesicouterine Ligament during Laparoscopic Radical Hysterectomy.

Background/Aims: The study aims to prevent serious urologic injury during a radical hysterectomy; we propose that one of the most important procedural steps is the careful management of the vesicouterine ligament (VUL). Patients and Methods: Between January 2013 and October 2014, we used a novel internal retractor in 17 patients undergoing a laparoscopic radical hysterectomy (LRH) for early-stage cervical cancer to obtain and secure a better surgical view. For management of the VUL during the laparoscopic procedure, we routinely used an internal retractor (EndoGrab; Virtual Ports, Misgav, Israel) and vessel tape to reposition the ureter in a safe lateral-caudal direction. Results: Using an EndoGrab, we were easily able to reproduce a suitable surgical view that simulated the one obtained by an abdominal route for radical hysterectomy. Using this improved laparoscopic procedure, we completed radical hysterectomies in all 17 cases without a ureteral injury complication. Conclusion: Our modified method using an EndoGrab is effective for the prevention of ureteral injury during a LRH, and its ease of use makes it suitable even for those surgeons early in their laparoscopic learning curve.

A Case of Extragonadal Teratoma in the Pouch of Douglas and Literature Review.

Mature cystic teratoma is a germ cell tumor of the ovaries and is often observed in clinical practice. However, extragonadal teratomas are rare tumors and have been reported outside the ovaries, (e.g., in the greater omentum). The mechanism underlying the development of extragonadal teratomas remains unknown. We encountered a case of extragonadal teratoma in the pouch of Douglas that appeared to be a parasitic dermoid cyst. From our experience and the literature review, we discuss the potential mechanism leading to the development of extragonadal teratomas. A 41-year-old nonpregnant woman was referred to our department due to myoma and anemia. A 4-cm asymptomatic mass in the pouch of Douglas was observed, and the patient was diagnosed with ovarian mature cystic teratoma. She underwent laparoscopic surgery, and intraoperative findings revealed that the fallopian tube was injured and torn, and a residual small ovary was observed in the left side of the ovary. A tumor measuring approximately 4 cm observed in the pouch of Douglas was extracted without rupturing. The tumor was diagnosed as a parasitic dermoid cyst by macroscopic and histopathological findings. Auto-amputation could be the underlying mechanism that leads to an isolated parasitic dermoid cyst in the pouch of Douglas.

Significance of abnormal peritoneal cytology on survival of women with stage I–II endometrioid endometrial cancer

OBJECTIVE To examine survival of women with stage I-II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). METHODS This is a multi-center retrospective study examining 1668 women with stage I-II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. RESULTS Malignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P<0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P<0.001) and cause-specific survival (hazard ratio 3.42, P=0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P=0.001) but not local-recurrence (5.2% versus 3.0%, P=0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P<0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P=0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P=0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P=0.63). CONCLUSION Our study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I-II endometrioid endometrial cancer, particularly for low-risk group.

Descriptive epidemiological study of vaginal cancer using data from the Osaka Japan population-based cancer registry: Long-term analysis from a clinical viewpoint

Abstract Vaginal cancer is such a rare tumor that epidemiological and clinical information for it is based mainly on studies of small numbers of cases. The aim of the present study was to perform a descriptive epidemiological analysis of vaginal cancer using a significantly larger population-based dataset from the Japanese Osaka Cancer Registry. The age-standardized incidence of vaginal cancer per 1,000,000 persons, from 1976 to 2010, was calculated and examined for trends. Relative-survival analysis was applied to estimate a more up-to-date 10-year period calculation, using data from recently followed-up patients. The conditional 5-year survival of patients who survived for 0 to 5 years after diagnosis was calculated. A total of 481 cases of vaginal cancer were registered in Osaka during the 35-year period from 1976 to 2010. The age-adjusted incidence rate has significantly and consistently decreased over this time [annual percent change (APC) = −1.29, 95% confidence interval (95% CI): −0.3 ∼ −2.2]; however, due to significant population aging, the raw incidence of vaginal cancer appeared to have been increasing. The 10-year relative survival of patients with surgery-based treatments was comparable to that of radiation-based treatments, implying that surgery and radiotherapy provide similar therapeutic benefits (P = .98). The 10-year relative survival was not significantly different during the period of 1976 to 2000 compared with the period of 2001 to 2008, although there has been, in the latter period, a tendency for improvement of long-term survival, especially for survival longer than 5 years. The longer the time after diagnosis, the higher the conditional 5-year relative-survival at 0 to 4 years after diagnosis. The age-adjusted incidence of vaginal cancer has decreased since 1976. Regrettably, the 10-year survival rate did not similarly improve, and it remained stable during the period from 2001 to 2008, compared with the period from 1976 to 2000, indicating that significant work remains to be done to develop more effective vaginal cancer treatments.

Total laparoscopic hysterectomy for endometrial cancer in a renal transplantation patient receiving peritoneal dialysis: Case report and literature review

Improved surgical techniques and immunosuppressant medications for organ transplantation have resulted in a significant increase in the number of women undergoing renal transplantation. Peritoneal dialysis (PD), a common supportive therapy for chronic renal failure, is also used in cases of renal transplantation failure. Herein, we report the first case of a rare total conventional laparoscopic gynecologic hysterectomy performed for endometrial cancer in a patient undergoing life‐supportive PD as a result of renal transplantation failure. No unusual intraoperative complications were experienced, but post‐surgical peritoneal leakage was observed. We reviewed the literature of alternative surgical methods of hysterectomy for endometrial cancer in patients who had undergone renal transplantation and were undergoing PD at the time of the hysterectomy. Laparoscopic hysterectomy could be safe in a renal transplantation patient receiving PD if injury to the transplanted ureter and renal artery is avoided by recognizing the patients anatomy and PD leakage is averted by careful peritoneum suture and avoiding contact with the PD catheter.

A case of laparoscopic surgery for endometrial cancer in a patient previously treated with a transvaginal mesh procedure for pelvic organ prolapse

Transvaginal mesh (TVM) surgery is an effective treatment option for women with pelvic organ prolapse (POP). Because the TVM procedure preserves the uterus, it is possible for endometrial cancer to occur at a later date. We herein present the first report of such an endometrial cancer, diagnosed well after TVM surgery for POP, and the use of laparoscopic surgery to conduct a simple total hysterectomy to treat it.

‘Smartscopy’ as an alternative device for cervical cancer screening: a pilot study

The use of smartphones, mobile networks and associated health applications (known as apps) is now almost universal. Countries with low medical resources need assistance in their delivery of healthcare. This is particularly true where there are limited numbers of specialised physicians or nurses with respect to cancer screening. As smartphones become more universal, real-time and near-real-time expert medical consultations and telediagnosis are becoming more common. This leads us to believe that there will soon be a demand for mobile cancer screening services, which will be particularly useful for women living in rural areas or doctor-less inner city communities. The smartphone would seem to have almost limitless possibilities to address this need. As a first step in studying how cervical cancer screening using a smartphone could have widespread implementation, we conducted a pilot study to evaluate the utility of a smartphone to diagnose cervical intraepithelial neoplasm or invasive cervical cancer in 20 patients having an abnormal cervical cytology. Our results indicate that continuing progress in digital imaging devices may allow the quality of cervical cancer screening to be improved.

Abstract 2153: ATP7B is a promising therapeutic target for uterine leiomyosarcoma

Objective Resistance to platinum drugs remains a significant problem in uterine leiomyosarcoma (LMS). We investigated the role of ATP7B in the resistance to platinum drugs in LMS using both in vitro and in vivo models. Methods The expression of the typical platinum transporters (MDR1, MRP2, ATP7A, and ATP7B) was examined in LMS cell lines using Western blotting analysis. ATP7A expression was investigated by immunohistochemistry (IHC) using clinical samples of LMS. IC50 values to cisplatin were measured in SK-LMS cells, SK-LMS-ATP7B-suppressed cell line (SK-LMS-7B cells), which permanently transfected PRS ATP7B shRNA vector. We established xenografted mice by inoculating SK-LMS cells and SK-LMS-7B cells, and examined in vivo platinum sensitivity with cisplatin for both tumors. This study was approved by the Institutional Review Board and the Ethics Committee of the Osaka University Hospital (approval #10302, approved on March 11, 2011). Results The expression of ATP7B was identified in the SK-LMS cells. ATP7B expression was identified in 70% (14/20) of the LMS clinical samples using IHC. The IC50-values to cisplatin improved from 17 mM to 4.3 mM after the suppression of ATP7B in SK-LMS-7B cells. A significant anti-tumor effect of cisplatin was observed in SK-LMS-7B xenografted mice than in SK-LMS xenografted mice. We also identified CuSO4 as an preferentially inhibitor of ATP7B in vitro. Conclusion ATP7B is associated with platinum resistance. CuSO4 acting as an inhibitor of ATP7B can be a therapeutic target for LMS. Citation Format: Mamoru Kakuda. ATP7B is a promising therapeutic target for uterine leiomyosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2153.