Liquid-based endometrial cytology using SurePath™ is not inferior to suction endometrial tissue biopsy for detecting endometrial malignancies: Midterm report of a multicentre study advocated by Japan Association of Obstetricians and Gynecologists.

OBJECTIVE: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach. METHODS: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics. RESULTS: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant. CONCLUSIONS: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale.

Clinical usefulness of the oral chemotherapy agent S-1 in heavily pre-treated patients with advanced or recurrent cervical cancer.

PURPOSE: Our aim was to evaluate the efficacy and safety of S-1 in heavily pre-treated patients with advanced (FIGO stage IVB) or recurrent cervical cancer. METHODS: The Institutional Review Board of our hospital approved the protocol for this retrospective phase II study. Patients with measurable disease received two oral doses of S-1 (35 mg/m(2)) daily for 4 weeks of a 6-week cycle or 2 weeks of a 3-week cycle. The antitumor effect, time to progression, overall survival, and adverse events were investigated. RESULTS: We retrospectively analyzed relevant data of 28 patients with advanced or recurrent cervical cancer. Twenty-two patients had prior chemotherapy (not including chemoradiotherapy) and 27 had prior radiotherapy. The median number of prior chemotherapy regimens and cycles was 2 (range 0-4) and 7 (range 0-35), respectively. Two patients (7.1%) had partial response, and 10 patients (35.7%) had stable disease. Ten patients (35.7%) discontinued the therapy because of progressive disease. The response in 5 patients could not be evaluated because of termination of treatment in the middle of the first cycle. The disease control rate was 42.8%. After a median follow-up duration of 7.5 months, the median time to progression was 4.2 months (95% CI 2.7-5.4) and the median overall survival was 9.92 months (95% CI 9.20-NA). The two patients with partial response had received less prior chemotherapy. CONCLUSIONS: Oral S-1 in palliative chemotherapy is a useful and well-tolerated treatment in heavily pre-treated patients with advanced or recurrent uterine cervical cancer.

Clinical features of long-term survivors of recurrent epithelial ovarian cancer.

BACKGROUND: Although recurrent epithelial ovarian cancer (EOC) is generally regarded as an incurable disease, some patients survive more than 5 years after the first recurrence. The aim of this study was to evaluate the clinical features of patients with recurrent EOC who achieve long-term survival. METHODS: We retrospectively reviewed the medical records of 164 patients with recurrent EOC and analyzed the clinical stage, histologic subtype, primary treatment, disease-free interval (DFI), recurrence site, secondary treatment, and overall survival from the time of the first recurrence (R-OS), using the Kaplan-Meier method and the log-rank test. RESULTS: The median R-OS for all 164 patients was 25 months and the 5-year R-OS rate was 25.4 %. There were no significant differences in R-OS according to the disease stage. The median R-OS was significantly shorter in the 6-12-month DFI group (23 months) than in the ≥12-month DFI group (61 months) (p = 0.0002), while there was no significant difference between the 6-12 and 3-6-month DFI groups (20 months) (p = 0.161). Of the 164 patients, only 14 survived >5 years after the first recurrence. Most of them underwent surgery and/or radiotherapy in combination with chemotherapy and underwent >18 cycles of platinum-based chemotherapy throughout their treatments (median 22 cycles; range 4-44). CONCLUSIONS: If high sensitivity to platinum is maintained, patients with recurrent EOC may have prolonged survival following repeated platinum-based chemotherapy cycles. Moreover, their prognosis improves when chemotherapy is combined with secondary cytoreductive surgery and/or irradiation.

Adjuvant chemotherapy for stage I clear cell carcinoma of the ovary: an analysis of fully staged patients.

OBJECTIVE: Although postoperative adjuvant chemotherapy is generally recommended for early-stage ovarian cancer, it remains unclear whether adjuvant chemotherapy is also effective for clear cell carcinoma (CCC). METHODS: Seventy-three patients with stage I CCC of the ovary who had undergone complete surgical staging formed the study population (stage IA, 20 patients; stage IC, 53 patients). Survival and multivariate analyses were retrospectively performed to determine the effectiveness of postoperative chemotherapy in these patients. RESULTS: Of the total (73 patients), 30 patients received adjuvant chemotherapy (stage I C-positive), whereas 43 patients did not (stage I C-negative). The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates for the stage I C-positive group were 80.1% and 87.4% compared with 73.9% and 81.7% for the stage I C-negative group. The differences in survival between these groups were not significant (PFS: P = 0.610; OS: P = 0.557). Four of the patients with stage IA CCC underwent chemotherapy, whereas the remaining 16 patients received no additional therapy. No recurrence was observed in either group. Of the patients with stage IC CCC, 26 patients underwent chemotherapy (stage IC C-positive) and 27 received no additional therapy (stage IC C-negative). There was no statistical difference in PFS and OS between the stage IC C-positive and stage IC C-negative groups. Of the patients with stage IC without artificial rupture, the 5-year PFS rates of the C-positive and C-negative patients were 69.6% and 34.6%, respectively, but the 5-year OS rates were 75.0% and 70.0%, respectively (not significant). Multivariate analyses confirmed that the presence or absence of adjuvant chemotherapy was not a prognostic indicator. CONCLUSIONS: The current study was performed only in fully staged patients, suggesting that postoperative adjuvant chemotherapy is not necessary for stage IA CCC patients. For patients with stage IC CCC patients, adjuvant chemotherapy suppressed recurrence, but the effectiveness was insufficient in our limited study. Further studies are required to clarify this.

Parametrial involvement in FIGO stage IB1 cervical carcinoma diagnostic impact of tumor diameter in preoperative magnetic resonance imaging.

BACKGROUND: In the surgical treatment for early-stage cervical carcinoma, it is important to identify preoperatively a low-risk group of patients as candidates for less radical surgery to avoid the morbidity associated with radical hysterectomy. The aim of this study was to evaluate the correlation between tumor diameter measured preoperatively using magnetic resonance imaging (MRI) and pathological prognostic factors in International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical carcinoma. METHODS: A total of 125 patients with FIGO stage IB1 cervical cancer were included in this study. Clinical records, pathology reports, and MRI findings were retrospectively reviewed. RESULTS: Histological diagnosis was squamous cell carcinoma in 57 patients and non squamous cell carcinoma in 68 patients. All patients underwent preoperative evaluation by MRI within a median period of 13.5 days before surgery. The tumor diameter measured by MRI ranged from zero (no tumor detected) to 42 mm, with a median of 23 mm.Pathological prognostic factors included parametrial involvement, lymph node metastasis,deep stromal invasion, and lymphovascular space invasion. All these factors were found less frequently in patients with a smaller tumor diameter. Most notably, parametrial involvement was seen in none of the patients with tumors 20 mm or less and was detected only in patients with tumors greater than 20 mm (P = 0.01). CONCLUSIONS: In the FIGO stage IB1 cervical carcinoma, the tumor diameter measured preoperatively by MRI correlates well with other pathological prognostic factors, especially with parametrial involvement. This finding suggests that the tumor diameter measured in preoperative MRI may serve as a strong predictor of parametrial involvement in FIGO stage IB1 cervical carcinoma, which can be used to select a candidate population for less radical surgery without the need for a cone biopsy before hysterectomy.

Neoadjuvant chemotherapy followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for Stage IB2-IIB cervical cancer--irinotecan and platinum chemotherapy.

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Forty-six consecutive patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy plus postoperative chemotherapy. Median (range) body mass index (BMI) of the patients was 20.2 (16.2-26.4). Regimens for NAC and postoperative chemotherapy were irinotecan and cisplatin (CPT-11/CDDP) or CPT-11 and nedaplatin (CPT-11/NDP). A total of six cycles of NAC and postoperative chemotherapy were prescribed. No use of radiotherapy was scheduled, except in the case of a recurrence. RESULTS: With a median follow-up period for survivors of 38.8 months (range 24-54 months), the 2- and 3-year progression-free survival rates were 91.2% and 86.1%, respectively. Overall response rate of NAC was 80.4%. Recurrence was observed in seven patients. In the absence of radiotherapy, pelvic recurrence was observed in only three patients; another two had para-aortic lymph nodes and the remaining two distant metastases. Toxicities due to chemotherapy were generally tolerable. Postoperative complications included urinary fistula (four patients, 8.7%) and bowel obstruction (two patients, 4.3%), all of which required surgical intervention. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. Although a relatively large incidence of postsurgical complications was observed among low-BMI patients, this treatment offers the advantage of minimizing radiation-induced morbidity, allowing radiotherapy to be reserved for the possible event of pelvic recurrence.

Oral leukoplakia, a precancerous lesion of squamous cell carcinoma, in patients with long-term pegylated liposomal doxorubicin treatment.

Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term use has been associated with development of squamous cell carcinoma of the tongue and oral cavity (SCCTO) in some patients. The study objective was to estimate the prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with ovarian cancer and long-term PLD use.After approval of the institutional review board, medical record of 114 patients who were treated with PLD at our institution between January 2010 and December 2016 were retrospectively reviewed. All those patients have been referred for routine monitoring of oral mucositis every time before administration by a dentist. The patient characteristics included in the evaluation were age, smoking and drinking habits, the PLD dose and schedule, and presence or absence of oral leukoplakia and SCCTO at each oral examination. The relationships of the incidence of oral leukoplakia and patient characteristics were analyzed.The median total PLD dose was 160 (range 40-1550) mg/m. Oral leukoplakia was seen in 6 (5.3%) patients. The median PLD dose, at the time of oral leukoplakia diagnosis, was 685 (range 400-800) mg/m. SCCTO was not found. Univariate analysis revealed that age, Brinkman index, and habitual drinking were not considered as risk factors for oral leukoplakia, and only total PLD dose (OR, 1.470; 95% CI, 1.19-1.91; P < .001) remained as a significant independent risk factor for oral leukoplakia. The ROC curve analysis indicated that the optimal cutoff value of the total PLD dose to predict development of oral leukoplakia was 400 mg/m. The sensitivity was 100% and the specificity was 88.8%. No patient discontinued PLD because of oral leukoplakia or SCCTO.The 2 most important clinical observations were the occurrence of oral leukoplakia in patients with long-term PLD use and that the development of oral leukoplakia was related to a total cumulative dose ≥400 mg/m. Routine oral surveillance is recommended, particularly when the cumulative total dose exceeds 400 mg/m.

Patient-perceived satisfaction after definitive treatment for men with high-risk prostate cancer: radical prostatectomy vs. intensity-modulated radiotherapy with androgen deprivation therapy.

OBJECTIVE: To assess the change in disease-specific health-related quality of life and to evaluate patient-perceived satisfaction after radical prostatectomy (RP) or intensity-modulated radiotherapy (IMRT) with androgen deprivation therapy (ADT) for patients with high-risk prostate cancer (PCA) that has been defined by the European Association of Urology guideline. METHODS: Between 2006 and 2010, 150 patients with high-risk PCA who underwent either RP (n = 97) or IMRT with ADT (n = 53) were enrolled in this prospective health-related quality of life study. Disease-specific health-related quality of life at baseline, 3, 6, 12, and 24 months and patient-perceived satisfaction at 12 and 24 months after these treatments were estimated using the Expanded Prostate Cancer Index Composite. RESULTS: Urinary bother and irritation and obstruction scores did not change significantly between both treatment groups throughout the 2-year follow-up. ADT greatly influenced sexual and hormonal functions and bothers in patients who received IMRT with ADT. The patient-perceived satisfaction at 12 months after the treatments was approximately 80% in both treatment groups, and there was no significant difference between the 2 groups. At 12 months after the treatments, urinary function (P = .001) was identified as the most significant predictor of patient-perceived satisfaction, although it was not associated with the treatment type. CONCLUSION: The majority of patients with high-risk PCA who received RP or IMRT with ADT reported high patient-perceived satisfaction after the treatments. This study showed that improvement in urinary function might contribute to patient-perceived satisfaction after the treatments.

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment.

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter ("small endometrial carcinoma") were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of "small endometrial carcinomas" were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most "small endometrial carcinomas" arise in the upper third of the corpus, careful endometrial sampling there is important for early detection.