Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.

BACKGROUND: Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome. METHODS: Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm. RESULTS: The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes. CONCLUSION: Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy.

Malignant Pericardial Tamponade Secondary to Ovarian Clear Cell Carcinoma.

Malignant pericardial effusion is an uncommon metastatic manifestation of ovarian carcinoma. Few cases of ovarian serous carcinoma have been previously reported. Ovarian clear cell carcinoma is the second most common histologic subtype in East Asian countries and is a relatively rare in Western countries. Here, we report the case of cardiac tamponade secondary to Ovarian clear cell carcinoma. A 46-year-old woman with recurrent Ovarian clear cell carcinoma presented with worsening cough, palpitations, and shortness of breath during chemotherapy. Chest radiography and computed tomography confirmed a pleural effusion with cardiac tamponade. The patient underwent pericardial fenestration and drainage for cardiac tamponade. Pericardial fluid cytology showed malignant cells forming papillary and ball-like clusters with irregular stacking. The cells had a mirror ball-like appearance and collagenous stroma, in which a homogenous hyaline core was observed in the center of most tumor cell clusters. Based on these findings, a diagnosis of Ovarian clear cell carcinoma metastasis was made. She received palliative care and died 5 months after the operation without recurrent cardiac tamponade. This case suggests that cytological findings from pericardial effusion are useful in diagnosing Ovarian clear cell carcinoma metastasis.

Prognostic Value of Human Papillomavirus Genotyping before and after Cervical Conization for Squamous Intraepithelial Lesion.

INTRODUCTION: We previously reported that preoperative human papillomavirus (HPV) type 16/18 positivity and postoperative high-risk (HR)-HPV test positivity are associated with abnormal postoperative cytology. In this study, we further examined whether preoperative and postoperative HR-HPV genotyping could predict cytological abnormalities and the risk of additional surgery. METHODS: Patients who underwent cervical conization at our hospital between July 2009 and June 2018 were enrolled. HPV genotyping was performed preoperatively for all patients with HPV-positive. The association among preoperative and postoperative HR-HPV genotyping results, the cumulative risk of cytological abnormalities, and additional surgery were evaluated. The endpoint approach was used to investigate the cumulative incidence of additional surgery owing to cytological abnormalities, such as low-grade squamous intraepithelial lesion positivity and recurrence 2 years after cervical conization. RESULTS: Positive and negative histological margins were observed in 21 and 287 of 308 cases, respectively. The cumulative incidence of abnormal cytology and additional surgery was significantly higher in margin-positive cases than that in margin-negative cases. Examination established according to the margin status demonstrated that the postoperative HR-HPV-positive group had a significantly worse prognosis than the HR-HPV-negative group. Additionally, 32 cases, wherein the same genotype detected before and after surgery, demonstrated significantly unfavorable outcomes. Fifteen patients with persistent HPV 16/18 had the worst prognosis than the other types. CONCLUSION: Preoperative and postoperative HR-HPV genotype tests were used to predict the cumulative incidence of abnormal cytology and additional surgery. Particularly, patients with suspected persistent HPV type 16/18 infection are at a high recurrence risk.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079).

OBJECTIVE: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. METHODS: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. RESULTS: Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. CONCLUSIONS: Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

Is Adjuvant Chemotherapy Necessary in Patients with Early Endometrial Cancer?

BACKGROUND: We investigated whether there was a difference in prognosis between patients with stage IA endometrial cancer with and without lymphovascular space invasion. METHODS: We enrolled patients with stage IA (pT1aN0M0) endometrial cancer admitted to our hospital from 2009 to 2018. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy. We immunopathologically evaluated the presence or absence of lymphovascular space invasion in the tumor tissue using hematoxylin and eosin, Elastica-van Gieson, and podoplanin staining. We analyzed disease-free and overall survival and calculated patients' survival distribution using the Kaplan-Meier method and log-rank test. The multivariate analysis was performed to determine the prognostic factors. RESULTS: A total of 116 patients were included. The median age of the patients was 57 (range, 30-78) years, and the histological subtype revealed 98 and 18 cases of types 1 and 2, respectively. The median follow-up period was 71.9 (range, 10.8-149) months, and the 3-year disease-free and 3-year overall survival rates were 94% and 99%, respectively. The disease-free and overall survival rates were significantly shorter in type 2 patients than in type 1 patients (type 2 vs. type 1; 77% vs. 97%, P < 0.01, 94% vs. 100%, P = 0.014, respectively). The univariate and multivariate analyses showed that there were no significant differences in disease-free survival between the lymphovascular space invasion-positive and -negative groups among type 1 cases. CONCLUSION: There was no difference in prognosis between patients with stage IA and type 1 endometrial cancer with and without lymphovascular space invasion.

Endometrial Cancer Arising in Adenomyosis That Could Not Be Diagnosed by Endometrial Biopsy: A Case Report.

Uterine adenomyosis is an estrogen-dependent tumor and one of the most common benign diseases in sexually mature women. The frequency of endometrial cancer associated with adenomyosis has been reported to be 18%-66%. On the other hand, endometrial cancer arising in adenomyosis (EC-AIA) is extremely rare. EC-AIA is now considered a different entity from and has a worse prognosis than endometrial cancer with adenomyosis (EC-A). In the present study, we report a case of endometrial cancer with adenomyosis in which endometrial biopsy failed to provide a definitive diagnosis. A 63-year-old female patient presented with endometrial thickening. Endometrial cytology was positive, and magnetic resonance imaging (MRI) showed small lesions suggestive of endometrial cancer with shallow invasion and adenomyosis. However, an endometrial biopsy showed only metaplasia, and careful follow-up was initiated. Subsequent endometrial cytology showed enlarged and round nuclei, uniform chromatin distribution, no thickening of nuclear margins, and abundant cytoplasm appearing in a sheet-like arrangement, suggesting atypical cells of endometrial glands with metaplasia. Three suspicious positive results and one positive result were observed, but repeated biopsies did not lead to the diagnosis of malignancy. The patient underwent diagnostic hysterectomy 19 months after the initial visit. The postoperative histopathological diagnosis was stage IA endometrial cancer (endometrioid carcinoma G1). This case of endometrial cancer associated with adenomyosis was difficult to diagnose. Our findings demonstrate that EC-AIA should be considered even if no lesions were detected by endometrial biopsy.

Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma.

This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

A simplified procedure of nerve-sparing radical hysterectomy.

AIM: We devised a simplified nerve-sparing radical hysterectomy that is simpler than commonly used procedures. METHODS: We retrospectively examined 16 cases of classical non-nerve-sparing radical hysterectomy (non-nerve-sparing group) and 16 cases of simplified nerve-sparing radical hysterectomy (nerve-sparing group) performed between 2019 and 2020. We examined and compared the duration of surgery, blood loss, perioperative complications, postoperative urinary function (presence or absence of urinary sensation, number of days with residual urine measurement, and frequency and duration of oral sustained release urapidil capsules and self-catheterization), and short-term prognosis between the two groups. RESULTS: Compared to conventional non-nerve-sparing radical hysterectomy, the duration of surgery for nerve-sparing radical hysterectomy was significantly shorter (407 [339-555] min vs. 212 [180-356] min; p < 0.001), and blood loss was significantly less. Compared to the nerve-sparing group, the non-nerve-sparing group had more cases of oral urapidil use and a higher frequency of clean intermittent catheterization. Clean intermittent catheterization was required in two cases in the nerve-sparing group; however, it was withdrawn at 180 and 240 days. Conversely, clean intermittent catheterization was still required in three cases in the non-nerve-sparing group. There were no statistically significant differences in progression-free survival and overall survival between the two groups. CONCLUSION: The simple nerve-sparing radical hysterectomy resulted in shorter duration of surgery and less blood loss as well as in a clear improvement in the postoperative urinary status and short-term prognosis. This technique simplifies nerve-sparing radical hysterectomy, which is commonly thought to be complicated, making it easier to understand.

Is cytology/HPV co-testing for cervical cancer screening useful in Japan?

OBJECTIVE: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan. METHODS: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated. RESULTS: The data of 297 970 women (182 697 for cytology-based, 115 273 for co-testing) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P < 0.001, P < 0.0001, P < 0.01, respectively). Between ages 25-49, CIN2+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Between ages 30-49, CIN3+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). CONCLUSION: Limiting the target age group may minimize the possible harm of screening. Cytology/HPV co-testing may be useful in Japanese populations if balance is maintained between benefit and harm.

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Amide proton transfer imaging in differentiation of type II and type I endometrial carcinoma: a pilot study.

PURPOSE: This study aimed at evaluating the efficacy of amide proton transfer (APT) imaging in differentiation of type II and type I uterine endometrial carcinoma. MATERIALS AND METHODS: Thirty-three patients diagnosed with uterine endometrial carcinoma, including 24 with type I and 9 with type II carcinomas, underwent APT imaging. Two readers evaluated the magnetization transfer ratio at 3.5 ppm [MTRasym (3.5 ppm)] in each type of carcinoma. The average MTRasym (APTmean) and the maximum MTRasym (APTmax) were analyzed. The receiver operating characteristic (ROC) curve analysis was performed. RESULTS: The APTmax was significantly higher in type II carcinomas than in type I carcinomas (reader1, p = 0.004; reader 2, p = 0.014; respectively). However, APTmean showed no significant difference between type I and II carcinomas. Based on the results reported by reader 1, the area under the curve (AUC) pertaining to the APTmax for distinguishing type I from type II carcinomas was 0.826, with a cut-off, sensitivity, and specificity of 9.90%, 66.7%, and 91.3%, respectively. Moreover, based on the results reported by reader 2, the AUC was 0.750, with a cut-off, sensitivity, and specificity of 9.80%, 62.5%, and 87.5%, respectively. CONCLUSION: APT imaging has the potential to determine the type of endometrial cancer.

Re-classification of uterine cervical cancer cases treated with radical hysterectomy based on the 2018 FIGO staging system.

OBJECTIVE: We re-classified patients with stage IB-II disease (based on the 2008 system) and compared the outcomes with those obtained after using the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. MATERIALS AND METHODS: We reviewed the data of 154 patients with cervical cancer who underwent radical hysterectomy at our hospital during 2006-2016. Pathological, histological, and radiographic data were used to re-classify the cases based on the 2018 FIGO system. We compared these outcomes to those obtained after using the 2008 FIGO assignments. Overall survival (OS) was calculated from primary therapy initiation until death or the last follow-up examination. RESULTS: The histological types were squamous cell carcinoma (108 cases) and others (46 cases). The 2008 FIGO system assignments were stage IB1, IB2, IIA1, IIA2, and IIB (87, 27, seven, five, and 28 patients, respectively). The new 2018 FIGO system assignments were stage IB1, IB2, IB3, IIA1, IIA2, IIB, and IIIC1 (52, 26, 16, six, three, 21, and 30 patients, respectively). Re-classification to stage IIIC1 disease was observed for previously assigned stage IB1, IB2, IIA1, IIA2, and IIB cases (10, seven, two, two, and nine cases, respectively). The median OS durations based on the 2018 FIGO system were 71.7, 61.1, and 62.3 months for patients with stage IB1, IB2, and IB3 (p = 0.04) disease, respectively. The new stage IB3/IIA2/IIB cases had longer OS than the old stage IB2/IIA2/IIB cases. A positive computed tomography (CT) finding of nodal involvement was observed in 37% of cases with pathological confirmation of pelvic lymph node (LN) involvement. Using CT to identify pelvic LN metastasis had a sensitivity of 37% and specificity of 93%. CONCLUSION: The 2018 FIGO staging system for cervical cancer after radical hysterectomy showed a better ability to differentiate survival outcomes. However, the image evaluation method should be reconsidered.

Differential expression of estrogen receptor subtypes in ovarian high-grade serous carcinoma and clear cell carcinoma.

PURPOSE: To investigate the role of estrogen receptors (ERs) in high-grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) of the ovary and evaluate ERs as prognostic biomarkers for ovarian cancer. METHODS: This study included 79 patients with HGSC (n = 38) or CCC (n = 41) treated at our institution between 2005 and 2014. Immunohistochemistry examined protein expression of ERα, ERß, and G protein-coupled estrogen receptor-1 (GPER-1); relationships between ERα, ERß, and GPER-1 with patient survival were evaluated. Additionally, cell proliferation assay and phosphokinase proteome profiling were performed. RESULTS: In HGSC patients, expression of ERα, cytoplasmic GPER-1, or nuclear GPER-1 was associated with poor progression-free survival (PFS) (P = .041, P = .010, or P = .013, respectively). Cytoplasmic GPER-1 was an independent prognostic factor for PFS in HGSC patients (HR = 2.83, 95% CI = 1.03-9.16, P = .007). ER expressions were not associated with prognosis in CCC patients. GPER-1 knockdown by siRNA reduced the cells number to 60% of siRNA-control-treated cells (P < .05), and GPER-1 antagonist, G-15 inhibited two HGSC cell lines proliferation (KF and UWB1.289) in a dose-dependent manner. Phosphoprotein array revealed that GPER-1 silencing decreased relative phosphorylation of glycogen synthase kinase-3. CONCLUSIONS: High GPER-1 expression is an independent prognostic factor for PFS in HGSC patients, and GPER-1 may play a role in HGSC cell proliferation.

Evaluating the efficacy and safety of ureteral stent placement as a preoperative procedure for gynecological cancer surgeries: A retrospective cohort study.

AIM: To evaluate the efficacy and safety of ureteral stent placement (USP) as a preoperative procedure for gynecological cancer surgeries. METHODS: This was a single-institution retrospective cohort study of 259 patients with gynecological cancer who underwent laparotomy. In 126 patients (USP+ group), a ureteral stent was inserted into the bilateral ureters after the induction of general anesthesia. The remaining 133 patients (USP- group) did not undergo USP. We compared operation time, blood loss, and frequency of laparotomy-related perioperative urinary complications between the groups. The stent was removed 5-7 days postoperatively. Patients were evaluated for signs of hydronephrosis at discharge. The Fisher's exact test was used to investigate the significance of differences in patient characteristics, and multivariate analysis was performed using a Cox proportional hazards model. A p-value of <0.05 was considered statistically significant. RESULTS: There were no significant differences in age and body mass index between the groups. Two patients in the USP- group experienced intraoperative ureteral injury. Total operation time and blood loss were significantly increased in the USP+ group. The risk of bladder tamponade and postoperative hydronephrosis was influenced by USP. USP was unaffected by a history of abdominal surgery, stage of tumor progression, lymphadenectomy type, or hysterectomy type. CONCLUSIONS: The incidence of bladder tamponade and hydronephrosis postoperatively was significantly higher in patients with USP than in those without USP.

Phase II study of a new multidisciplinary therapy using once every 3 week carboplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy for locally advanced cervical cancer.

BACKGROUND: We proposed a novel treatment strategy, consisting of triweekly cisplatin plus dose-dense weekly paclitaxel before and after radical hysterectomy without adjuvant radiation therapy to treat locally advanced cervical cancer. However, cisplatin-related severe non-hematologic toxicities were frequent during this strategy. This study aimed to assess the applicability of replacing cisplatin with carboplatin in our proposed strategy. METHODS: Women with International Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB2, IIA2, or IIB cervical cancer received three cycles of carboplatin (based on an area under the curve of six), each 21 days apart, starting on day 1, and 80 mg/m2 of paclitaxel on days 1, 8, and 15 of each 21-day cycle before undergoing radical hysterectomy. Patients with one or more high-risk factors, including lymph vascular invasion, parametrial invasion, lymph-node metastasis, or positive margins, received three additional cycles of chemotherapy after hysterectomy. Concurrent chemoradiation therapy was only applied to those patients who failed to respond to neoadjuvant chemotherapy. RESULTS: Between September 2014 and July 2016, 50 women (13 women with FIGO stage IB2, 5 with stage IIA2, and 32 with stage IIB) were enrolled in this study. The overall response rate to chemotherapy was 92%, including 22% with pathological complete response. Forty-nine women (98%) completed the planned radical hysterectomy, and 11 (22%) women with one or more high-risk factors received three additional cycles of chemotherapy. Only four women (8%) received concurrent chemoradiation therapy after surgery. The 2- and 3-year progression-free survival rates were 88.0% and 83.8%, respectively, and the 2- and 3-year overall survival rates were 98.0% and 95.4%, respectively. Only two patients reported grade 3 or higher non-hematologic toxicities including grade 3 nausea in one patient and grade 3 liver dysfunction in one patient. CONCLUSIONS: Replacement the platinum agent resulted in equivalent efficacy, with reduced toxicity, in women with locally advanced cervical cancer. This strategy could considerably diminish the application of radiation therapy without reduced survival. A study to identify those patients who will benefit from this new multidisciplinary strategy is warranted.

Effects of pretreatment radiological and pathological lymph node statuses on prognosis in patients with ovarian cancer who underwent interval debulking surgery with lymphadenectomy following neoadjuvant chemotherapy.

AIM: To analyze whether radiological and pathological lymph node statuses affected prognosis in patients with epithelial ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery. METHODS: In total, 82 patients undergoing interval debulking surgery, including systematic retroperitoneal lymphadenectomy, were eligible for this study. We retrospectively analyzed the association among radiological diagnosed retroperitoneal lymphadenopathy by computed tomographic scan before (rLN) and after (yrLN) neoadjuvant chemotherapy, pathological lymph node metastasis (pLN) and prognosis. Patient survival distribution was calculated using the Kaplan-Meier method. RESULTS: There were 36 rLN+ cases (44%); there were no significant differences between rLN+ and rLN- with respect to progression-free survival and overall survival. Progression-free survival and overall survival did not differ between yrLN+ cases and yrLN- cases. Thirty-nine cases (47.5%) were pLN+, and both progression-free survival and overall survival were significantly shorter in pLN+ cases than in pLN- cases (P < 0.001 and P = 0.004, respectively). In univariate analysis, FIGO stage, pLN and surgical completion were prognostic factors for overall survival. Moreover, in multivariate analysis, pLN+ was the independent prognostic factor for progression-free survival (P = 0.001, 95% confidence interval: 1.911-15.69), and pLN and surgical completion were the only independent prognostic factors for overall survival (P = 0.046, P = 0.012). CONCLUSION: Radiological lymph node status may not be a prognostic factor in patients with ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery. Pathological lymph node metastasis affects progression-free survival and overall survival.

Implementation of primary HPV testing in Japan.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed. The objectives of the present study are to clarify in detail CIN2+ missed by this shift and to evaluate the feasibility of primary HPV testing in Japan. Data from 115,273 women who underwent co-testing with cytology and HPV testing in cancer screening were used in the current study. The cases with hrHPV-/≥LSIL ('hrHPV-/≥L-SIL' include CIN2-, in contrast, 'hrHPV-/≥L-SIL/CIN2+' doesn't include CIN2-) were analysed in detail. Women with hrHPV-/≥LSIL comprised 0.3% of the total. The prevalence of CIN2, CIN3, SCC or cervical adenocarcinomas in the lesions with HPV-/≥LSIL was 0.03% in the cancer screening group. Only one case of 14 cervical adenocarcinomas in ≥LSIL was hrHPV-. The prevalence of cancer missed by the shift in patients >50 years of age was significantly higher compared with patients younger than 49 years. In conclusion, the prevalence of CIN2+, which might be missed by the shift from primary cytology to primary HPV testing, was remarkably low in this Japanese cancer screening. The data indicated that primary HPV testing, which was more sensitive for CIN2+ than primary cytology, was a feasible method that can be used in Japan. In particular, primary HPV testing should be introduced for women <50 years old.

Long-term evaluation of renal function and neurogenic bladder following radical hysterectomy in patients with uterine cervical cancer.

OBJECTIVE: This study aimed to determine whether radical hysterectomy (RH) affects renal function. METHODS: Renal function was followed up in 83 patients with stage IB1-IIB cervical cancer who underwent RH during 2006-2015. Serum creatinine (sCre) levels were measured preoperatively and every year postoperatively. Estimated glomerular filtration rate (eGFR) was calculated using sCre levels. Patients who were unable to urinate by themselves or whose residual urine was ≥100 mL were referred to a urologist with the diagnosis of neurogenic bladder (NB). The relationship between NB occurrence and changes in sCre level or eGFR was evaluated respectively. RESULTS: Urological intervention was required in 45 patients (54.2%), and self-urethral catheterization was performed in 41 (49.3%) patients. The NB and clean intermittent catheterization (CIC) groups exhibited significant increases in sCre levels, which were not observed in the non-NB or non-CIC groups. In the non-NB group, eGFR did not change following surgery. However, in the NB group, significant decreases in eGFRs were observed at postoperative 2 and 3 years and at final follow-up. There was no difference in the incidence of cardiovascular events between patients with and without NB. CONCLUSION: In patients with NB following RH, a significant decrease in renal function was observed after postoperative 2 years.

Efficacy of panniculectomy-combined surgery in superobese patients with endometrial cancer: A case report and literature review.

INTRODUCTION: Panniculectomy is regarded as an effective approach in highly obese patients with endometrial cancer to improve surgical access or space of the surgical field. PRESENTATION OF CASE: A 66-year-old nulliparous woman was brought in from another hospital to our institute for newly diagnosed endometrial carcinoma. The patient was 158 cm in height and weighed 135.8 kg during the first visit to our hospital. Her body mass Index (BMI) was 54.4 kg/m2. Unfortunately, the patient developed an umbilical hernia and strangulation before the surgery. Emergency partial ileal resection and simple closure of the umbilical hernia were performed. We were finally able to perform simple hysterectomy, and bilateral salpingo-oophorectomy with panniculectomy. Her weight at the time of surgery was 115.5 kg which had been reduced by 20 kg from the time she was first brought in, and the BMI decreased from 54.4 to 45.3 kg/m2. The patient underwent follow-up without adjuvant therapy since she was in the low-risk group, and showed no signs of recurrence 12 months after surgery. DISCUSSION: There are various risks associated with surgery in highly obese patients. Diabetes mellitus, hypertension and smoking are reported to be risk factors of wound complication in panniculectomy, and it was reported that diabetes mellitus was an independent risk factor. CONCLUSION: The combination of panniculectomy was considered as an effective approach to perform safe surgery for obese patients.

Deep vein thrombosis and serum D-dimer after pelvic lymphadenectomy in gynecological cancer.

INTRODUCTION: Venous thromboembolism prevention during the perioperative period requires comprehensive risk-level assessment. The aim of this study was to evaluate the incidence of deep vein thrombosis and to assess the cut-off levels of serum D-dimer as a screening strategy for deep vein thrombosis during the perioperative period. METHODS: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were enrolled. We retrospectively analyzed the data on the cut-off value of D-dimer assessed using area under the receiver operating characteristic curve preoperatively, and 2 or 3 months, postoperatively. All patients underwent leg vein ultrasonography regardless of the serum D-dimer level. Furthermore, CT scans were performed to evaluate both disease status and venous thromboembolism, including pulmonary thromboembolism. Statistical analyzes were performed using the Mann-Whitney U-test (D-dimer values of each cancer), Chi-square test, Fisher's exact test (incidence of deep vein thrombosis), and one-way analysis of variance (patient characteristics). RESULTS: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were included in the analysis. Deep vein thrombosis rates were significantly higher in patients with ovarian cancer (P<0.001). The postoperative D-dimer value was significantly higher than the preoperative value. Postoperative D-dimer values were also significantly higher in patients who received adjuvant chemotherapy (P=0.001). The cut-off value of D-dimer was 1.55 µg/mL preoperatively (sensitivity, 48.0%; specificity, 94.1%), and this value was higher postoperatively, at 1.95 µg/mL (sensitivity, 37.0%; specificity, 90.9%). CONCLUSION: Postoperative D-dimer values are higher not only after surgery but also in patients who received adjuvant chemotherapy. The cut-off value of D-dimer at 2 or 3 months postoperatively was higher than preoperative value.