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The International Federation of Gynecology and Obstetrics (FIGO) staging system for Mullerian cancer was changed in 2014. Our objective was to evaluate the prognostic impact of stage IV subclassification in this new staging system, especially focusing on extra-abdominal lymph node metastasis. Eighty-two patients with stage IV Mullerian cancer treated between 2005 and 2016 at our hospital were retrospectively analyzed. Data for the following clinicopathological variables were analyzed: (1) FIGO stage; (2) tumor stage; (3) lymph node status; (4) histologic type; (5) neoadjuvant chemotherapy; (6) optimal surgery; and (7) bevacizumab use. Survival analysis was performed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. In accordance with the new classification, 28 and 54 patients were classified as FIGO IVA and IVB, respectively. In the Cox proportional hazards model, early-stage tumors (T1b–3b) and optimal surgery were statistically significant favorable prognostic factors. However, the new FIGO system did not discriminate prognostically between stage IVA and IVB. Median overall survival of stage IVB patients diagnosed with extra-abdominal lymph node metastasis only was better than that of stage IVA and stage IVB patients diagnosed with solid organ metastasis. In this analysis of the revised FIGO system of patients reclassified as FIGO stage IVA or IVB, no new prognostic information was obtained. There is a possibility that stage IVB patients diagnosed with extra-abdominal lymph node metastasis only can be classified as an earlier stage. Further modification of the FIGO staging system may be needed to improve the prediction of patient prognosis.

Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan. We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities’ experience with clinical research on SN biopsy. The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%). Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.

Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years. Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes. The mean patient age was 34 years (range 18–64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio [HR], 1.028; 95% CI 1.005–1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008–1.098; P = 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353–2.846; P = 0.0004). Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence.

To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12–146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.

High-dose chemotherapy for remission induction can induce cardiac toxicity prior to hematopoietic stem cell transplantation (HSCT). However, the details of cardiac function in patients undergoing HSCT are unclear, particularly during exercise. The aim of present study was to evaluate cardiac output responses to exercise in patients after high-dose chemotherapy before HSCT compared with in age-matched healthy controls. Twenty-nine patients before HSCT (age 44.6 ± 15.2 years) and 13 controls (45.8 ± 16.0 years) performed the 6-min walk test (6MWT). Cardiac output (CO), stroke volume (SV), heart rate (HR), and cardiac index (CI) were continuously measured during the 6MWT using the noninvasive thoracic impedance method. No significant difference was observed in the six-minute walk distance (6MD) between the two groups. SV, CO, and CI both at rest and the end of the 6MWT in the patients were significantly lower, compared with the controls, but there was no significant difference in HR. In all subjects, the 6MD was positively correlated with SV, CO, CI, and HR after the 6MWT. These findings suggest that cardiac output response to exercise indicates exercise intolerance, which may not be detected by 6MD in patients before HSCT.

Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy. We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed. We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients. Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies.

If the sentinel-lymph-node (SLN) concept is valid in cervical cancer, most patients could avoid pelvic lymphadenectomy when absence of metastasis is intraoperatively confirmed in the SLN. We assessed feasibility and accuracy of SLN detection using (99m)Tc phytate in patients with cervical cancer.Eighty-two women with stage Ia-IIb cervical cancer enrolled in this study. All underwent hysterectomy or trachelectomy with accompanying total pelvic lymphadenectomy. On the day before surgery, we injected fluid containing (99m)Tc-labeled phytate subepithelially into four cervical quadrants outside the tumor. Intraoperatively, SLNs were identified as radioactive "hot nodes" by gamma probe. Systematic bilateral pelvic lymphadenectomy was performed after the hot node sampling to evaluate the predictive ability of hot nodes.A total of 157 lymph nodes were detected as SLNs in 72 of 82 patients. SLN detection rate was 88%. Detection rate was 95% for the subgroups of patients with stage Ia-Ib1 disease and smaller tumor size (or=3 cm in maximal diameter). Lymph node metastasis was found in 15 patients. In 3 of them, no SLNs were detected. In the remaining 12 patients, each ipsilateral SLN contained metastasis when the pelvic lymph nodes contained metastases. Sensitivity was 100%, the false negative rate was 0%, and the negative predictive value of SLN was 100%.We conclude SLN detection using (99m)Tc-labeled phytate is satisfactory to assess pelvic nodes in patients with early cervical cancer; if validated with other research, it should be incorporated into clinical practice.

Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with “no vomiting”, “no significant nausea”, and complete response, respectively. Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of “no vomiting” patients (78.2 vs. 54.8 %; P

Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium. Forty patients with advanced endometrial cancer received postoperative adjuvant combination chemotherapy, using cisplatin (50 or 70 mg/m2), cyclophosphamide (500 mg/m2), and one of three anthracyclines (10 patients with doxorubicin [50 mg/m2], 18 with epirubicin [50 mg/m2], and 12 with pirarubicin [40 mg/m2]), from 1987 to 1999. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with pelvic lymph node dissection in 36 patients and paraaortic lymph node biopsy in 38 patients. Patients were considered eligible if they had adnexal metastasis, paraaortic lymph node metastasis, positive peritoneal cytology, or distant metastasis. The patients were divided into two groups: patients with no measurable lesion (group 1; n = 27), and those with residual measurable lesion (group 2; n = 13) after surgery. The response rate and progression-free survival rate were evaluated in group 2. In group 1, 7 patients (26%) had recurrence, and all of them died of the disease. No patients in stage IIIa (n = 10), however, had recurrence. In group 2, 6 of the 13 (46%) showed response to chemotherapy (complete response [CR], 31%; partial response [PR], 15%). Toxicity was moderate: 10 patients had grade 4 neutropenia; and dose reductions were mandated in 12 patients. In group 1, the survival of patients receiving chemotherapy was considered favorable, but patients with recurrent lesions had poor prognosis. On the other hand, in group 2, the efficacy of the chemotherapy was almost equal to that reported in the literature; however, this regimen did not contribute to an improvement in the survival rate. In conclusion, a new effective regimen of postoperative adjuvant therapy is highly desirable in patients with measurable residual lesions.

Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer. The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels. The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p