Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report.

BACKGROUND: Congenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3-9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case. CASE PRESENTATION: A 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses' umbilical cord, third fetus' placenta, and the fourth fetus' blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth. CONCLUSIONS: This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease.

Hereditary breast and ovarian cancer triggered by occult fallopian tube cancer: a case report.

BACKGROUND: At the time of benign gynecological surgery, a prophylactic salpingo-oophorectomy or salpingectomy is increasingly being performed concurrently to reduce the risk of future ovarian and fallopian tube cancer. We herein describe a case of hereditary breast and ovarian cancer syndrome in which a hysterectomy and bilateral adnexectomy were performed with a preoperative diagnosis of benign tumor. A detailed pathological examination revealed occult fallopian tube cancer, and additional staging surgery provided an accurate pathology diagnosis. CASE PRESENTATION: A 72-year-old Japanese woman with a past history of breast cancer underwent a hysterectomy and bilateral oophoro-salpingectomy for the preoperative diagnosis of uterine myoma and a right para-ovarian cyst. In the detailed pathological examination, high-grade serous carcinoma of the right fallopian tube was detected incidentally, and a subsequent staging laparotomy confirmed single para-aortic lymph node metastasis. Furthermore, a mutation in germline BRCA2 was detected postoperatively, and the patient was finally diagnosed with hereditary breast and ovarian cancer syndrome. She was diagnosed with fallopian tube cancer International Federation of Gynecology and Obstetrics Stage IIIA1(i) and started on adjuvant therapy (six courses of paclitaxel and carboplatin followed by maintenance therapy with olaparib), and 18 months after surgery, she was free of disease. CONCLUSION: This is a case of fallopian tube cancer that was diagnosed incidentally and then accurately staged with additional advanced staging surgery. Even in the absence of grossly malignant findings, a detailed pathological search of the fallopian tubes and accurate staging surgery are important to make the necessary treatment decisions for the patient.

Clinical perspectives of rare ovarian tumors: clear cell ovarian cancer.

Ovarian clear cell carcinoma (OCCC) is a rare and distinct histological type of epithelial ovarian carcinoma in terms of its histopathological, clinical and genetic features. Patients with OCCC are younger and diagnosed at earlier stages than those with the most common histological type-high-grade serous carcinoma. Endometriosis is considered a direct precursor of OCCC. Based on preclinical data, the most frequent gene alternations in OCCC are mutations of AT-rich interaction domain 1A and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. The prognosis of patients with early-stage OCCC is favorable, whereas patients at an advanced stage or who have the recurrent disease have a dismal prognosis due to OCCC's resistance to standard platinum-based chemotherapy. Despite a lower rate of response due to its resistance to standard platinum-based chemotherapy, the treatment strategy for OCCC resembles that of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and adjuvant platinum-based chemotherapy. Alternative treatment strategies, including biological agents based on molecular characteristics specific to OCCC, are urgently needed. Furthermore, due to its rarity, well-designed collaborative international clinical trials are needed to improve oncologic outcomes and the quality of life in patients with OCCC.

An attempt to establish real-world databases of poly(ADP-ribose) polymerase inhibitors for advanced or recurrent epithelial ovarian cancer: the Japanese Gynecologic Oncology Group.

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.

Frequency of thoracic recurrence based on pathological features in patients with ovarian epithelial tumors in stage I versus higher stages.

PURPOSE: The aim of this study was to clarify the frequency of thoracic recurrence and identify associated pathological features in postoperative patients with borderline or malignant ovarian epithelial tumors (BMOT) in stage I versus higher stages. MATERIALS AND METHODS: A total of 368 consecutive patients with a single primary BMOT were treated at our hospital. This study included the 217 patients with no residual disease on the first CT after standard treatment. The timing and pattern of recurrence on follow-up CT images with a scan range from chest to pelvis were evaluated retrospectively. Patient characteristics, tumor histology, and stage were recorded from electronic medical records. RESULTS: After a median follow-up period of 48 months, recurrence was detected by CT in 9 patients in stage I (n = 159) and 15 in stage II/III (n = 58) (p = 0.0001). Thoracic recurrence was detected in four patients in stage I and four in stage II/III (p = 0.15). Abdominal recurrence was identified as a factor associated with thoracic recurrence (P < 0.001). Clear cell carcinomas accounted for three out of four thoracic recurrences in stage I and two out of four in stage II/III, and had the highest rates of thoracic recurrence (7.7% in stage I and 22.2% in stage II/III) among all histological types associated with thoracic recurrence. Among patients with recurrence, thoracic recurrence-free probability (p = 0.38), median abdominal recurrence-free interval (18 vs 16 months; p = 0.55) and thoracic recurrence-free interval (16.5 vs 23 months; p = 0.89) did not differ significantly between stage I and stage II/III. CONCLUSION: The frequency and timing of thoracic recurrence did not differ significantly in postoperative patients with BMOT in stage I versus stage II/III. Abdominal recurrence and a histological type of clear cell carcinoma were most often associated with thoracic recurrence in stage I.

Malignant struma ovarii with thyroid-type papillary and poorly differentiated carcinoma: a case report.

BACKGROUND: Malignant struma ovarii is a very rare type of gynecologic cancer. Although its most common histological subtype is a pure type of papillary thyroid carcinoma containing two components, papillary carcinoma and poorly differentiated carcinoma, malignant struma ovarii is still extremely rare. As a result, the optimal treatment for this type of tumor remains uncertain due to its rarity. CASE PRESENTATION: A 62-year-old Japanese female presented with a pelvic tumor and clinical diagnosis of malignant tumor of the ovary. She underwent complete debulking surgery, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The histology of the ovarian tumor revealed malignant struma ovarii with thyroid-type papillary projections and poorly differentiated carcinoma. Because of the complete resection and the absence of distant metastasis, the patient did not receive any adjuvant therapy. At 24 months after surgery, she was free of disease. CONCLUSION: This is a rare case report of malignant struma ovarii, without recurrence, in which the component was papillary thyroid carcinoma mixed with poorly differentiated carcinoma. Foregoing adjuvant therapy might be one option for malignant struma ovarii in cases with complete resection and no distant metastasis. In addition, we should consider that long-term follow-up is needed for malignant struma ovarii.

Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy.

BACKGROUND: There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. METHODS: From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan-Meier log rank. RESULTS: A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. CONCLUSION: This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan.

BACKGROUND: The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. METHODS: We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. RESULTS: The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). CONCLUSION: More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

Oncologic outcomes for patients with endometrial cancer who received minimally invasive surgery: a retrospective observational study.

BACKGROUND: Laparoscopic hysterectomy has been performed for patients with endometrial cancer as minimally invasive surgery; however, the long-term outcomes of high-risk disease compared to open surgery remain unclear. METHODS: Eight hundred and eighty-three patients with endometrial cancer who underwent laparoscopic or abdominal hysterectomy were categorized into three groups. Low-risk disease was defined as stage IA disease with endometrioid carcinoma of grade 1 or 2. Uterine-confined disease was defined as stage IA disease with high-grade tumors or stage IB and II disease. Advanced disease was defined as stage III or IV disease. The progression-free survival (PFS) and overall survival (OS) rates were compared between laparoscopic and laparotomic hysterectomy. RESULTS: Among 478 patients with low-risk disease, including 226 with laparoscopy and 252 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 97.4% vs. 97.1%, p = 0.8; 3-year OS rate, 98.6% vs. 98.3%, p = 0.9). Among the 229 patients with uterine-confined disease, including 51 with laparoscopy and 178 with laparotomy, the prognosis was not significantly different between the groups (3-year PFS rate, 90.5% vs. 85.5%, p = 0.7; 3-year OS rate, 91.3% vs. 92.5%, p = 0.8). Among the 176 patients with advanced disease, including 24 with laparoscopy and 152 with laparotomy, laparoscopic hysterectomy had a higher PFS rate and OS rate than laparotomic hysterectomy (3-year PFS rate, 74.5% vs. 51.5%, p = 0.01; 3-year OS rate, 92.3% vs. 75.1%, p = 0.03). CONCLUSIONS: Laparoscopic procedures are not associated with a poorer outcome than laparotomy in patients with advanced endometrial cancer or uterine-confined endometrial cancer.

The Diagnostic Accuracy of an Intraoperative Frozen Section Analysis and Imprint Cytology of Sentinel Node Biopsy Specimens from Patients with Uterine Cervical and Endometrial Cancer: a Retrospective Observational Study.

Sentinel node biopsy (SNB) may be a decision-making tool for function preservation surgery, including radical trachelectomy and ovary preservation in the treatment of cervical and endometrial cancer. The intraoperative diagnosis is important for guiding treatment decisions for patients with these conditions. Three hundred seventy-one patients with cervical and endometrial cancer received SNB with an intraoperative frozen section analysis and imprint cytology. The sentinel node was cut in half, parallel to the longest axis, to obtain the maximum section area. After performing imprint cytology, one half was used to create a frozen section. The specimen was cut at 2-mm intervals into 5-µm-thick sections, which were subjected to hematoxylin and eosin staining. The diagnostic accuracy of intraoperative frozen section analyses and imprint cytology was compared to the final pathological diagnosis. Among 951 detected sentinel nodes, 51 nodes were found to be positive in the final pathological diagnosis. The sensitivity of a frozen section analysis, imprint cytology and the combination of the two modalities was 76.5%, 72.6%, and 92.2%, respectively. The specificity of a frozen section analysis and imprint cytology was 100%. The negative predictive value of a frozen section analysis and imprint cytology was 98.7% and 98.5%, respectively. In these settings, the accuracy of the frozen section analysis and imprint cytology in the evaluation of SNB specimens was considered acceptable; however, the sensitivity of the combined approach was higher in comparison to when a frozen section analysis or imprint cytology was performed alone.

Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is a leading cause of cancer-related death in women, and thus an accurate diagnosis of the predisposition and its early detection is necessary. The aims of this study were to determine whether serum exosomal microRNA-34a (miR-34a) in ovarian cancer could be used as a potential biomarker. METHODS: Exosomes from OC patients' serum were collected, and exosomal miRNAs were extracted. The relative expression of miR-34a was calculated from 58 OC samples by quantitative real-time polymerase chain reaction. RESULTS: Serum exosomal miR-34a levels were significantly increased in early-stage OC patients compared with advanced-stage patients. Its levels were significantly lower in patients with lymph node metastasis than in those with no lymph node metastasis. Furthermore, its levels in the recurrence group were significantly lower than those in the recurrence-free group. CONCLUSIONS: Serum exosomal miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC.

Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24-positive cells in ovarian cancer.

CD24, which is upregulated in several human malignancies, is related to Epithelial-mesenchymal-transition (EMT) and has characteristics of cancer stem-like cells, especially in cisplatin-resistant ovarian carcinoma cells. Drug delivery systems represent a promising therapeutic approach for diseases with treatment resistance, and the present study investigated a novel CD24-targeted drug delivery system for advanced ovarian carcinoma. We produced liposomal cisplatin with a red fluorescent substance - cyanine 5.5 (GL-CDDP-Cy5.5). In order to target CD24-positive cells, an anti-CD24 monoclonal antibody was modified to the above drug (CD24-GL-CDDP-Cy5.5). Specific uptake of CD24-GL-CDDP-Cy5.5 was confirmed using a therapeutically resistant ovarian cancer cell line, Caov-3 cells. Antitumor effects of CD24-GL-CDDP-Cy5.5 were then evaluated in Caov-3 ×enograft mice. CD24-GL-CDDP-Cy5.5 showed more specific uptake by flow cytometry than GL-CDDP-Cy5.5. In xenograft mice, GL-CDDP-Cy5.5 and CD24-GL-CDDP-Cy5.5 treatment had significantly higher platinum concentration in disseminated tumor cells than cisplatin (P<0.05). Moreover, CD24-GL-CDDP-Cy5.5 suppressed tumor growth and prolonged survival time compared with other treatments. Median survival times of the control, cisplatin, GL-CDDP-Cy5.5 and CD24-GL-CDDP-Cy5.5 groups were 37, 36, 46 and 54 days after inoculation, respectively. Immunohistochemical analysis showed that CD24-GL-CDDP-Cy5.5 treatment, compared with GL-CDDP-Cy5.5, decreased the number of CD24-positive cells and suppressed the EMT phenomenon significantly (P<0.05). The present study demonstrated that CD24-GL-CDDP-Cy5.5, compared with other treatments, improved therapeutic efficacy. The present results suggested the potential for targeting anticancer therapeutics for CD24-positive cells to prevent disease progression.

Urodynamic outcomes after pelvic nerve-sparing radical hysterectomy with or without neoadjuvant chemotherapy.

OBJECTIVE: Our purposes of this study were to characterize a group of bulky cervical cancer patients who underwent a nerve sparing radical hysterectomy (NSRH) with or without neoadjuvant chemotherapy (NAC), to compare surgical outcomes and the preservation of bladder function, and to compare prognoses. RESULTS: Fifty-three patients had NSRH without NAC (Group A), and 33 patients had NSRH after NAC (Group B). With regard to prognostic factors, there was only a significant difference between both groups with regard to lymph node metastasis (15% vs 42%, P = 0.01). Moreover, bladder function in Group B patients improved to the same extent as the preoperative rate three months postoperatively. These data were similar to the results in Group A. With regard to overall survival, the 5-year survival rate was 98.1% (95% confidence interval (CI) 87.8-99.7) in Group A and 86.7% (95% CI 71.7-96.7) in Group B (P > 0.1). METHODS: We retrospectively identified 86 patients with cervical cancer who underwent NSRH at Osaka Medical College from May 2009 to November 2016. NAC was performed via balloon occluded arterial infusion. We extracted data on the patient's stage of progress, tumor volume, histological subtype, bleeding volume, urodynamic study results, and postoperative complications. The data were divided into two groups - those patients who received NAC and those who did not - and then compared. CONCLUSIONS: According to our analysis, NSRH surgery after NAC via balloon occluded arterial infusion brings beneficial results to patients with bulky IB2 to IIB cervical cancers.

A rare case of ovarian carcinosarcoma with squamous cell carcinoma.

BACKGROUND: Ovarian carcinosarcoma, which contains sarcomatous and carcinomatous components, is a very rare tumor. The carcinomatous component is often adenocarcinoma, and squamous cell carcinoma is extremely rare. We herein report a case of ovarian carcinosarcoma in which the carcinomatous component was squamous cell carcinoma. CASE PRESENTATION: A 68-year-old woman presented with a huge ovarian tumor with a clinical diagnosis of malignant tumor of the ovary. She underwent hysterectomy, bilateral adnexectomy, omentectomy and lymphadenectomy. Histologically, the tumor cells showed undifferentiated pleomorphic sarcoma as the sarcomatous component and squamous cell carcinoma as the carcinomatous component. The final diagnosis was ovarian carcinosarcoma with squamous cell carcinoma in the carcinomatous component, stage IIIA1. Postoperatively, the patient was treated with six cycles of combination chemotherapy with paclitaxel and carboplatin as adjuvant therapy. The patient was free of disease at 45 months' follow-up consultation. CONCLUSION: This is a rare report of ovarian carcinosarcoma with an epithelial component composed of squamous cell carcinoma. Combination chemotherapy with paclitaxel and carboplatin may be an effective choice as adjuvant chemotherapy in cases of ovarian carcinosarcoma including squamous cell carcinoma.

A multi-institutional observational study on the effects of three-dimensional radiotherapy and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors.

BACKGROUND: The aim of this study was to evaluate the effects of treatment with both three-dimensional radiotherapy (3DRT) and weekly 40-mg/m2 cisplatin on postoperative uterine cervical cancer patients with high-risk prognostic factors. METHODS: We conducted a retrospective multi-institutional chart review of postoperative uterine cervical cancer patients with high-risk prognostic factors who had been treated with both 3DRT and weekly 40-mg/m2 cisplatin from 2007 to 2012. Each participating hospital provided detailed information regarding patient characteristics, treatment outcomes, and treatment complications. RESULTS: The eligible 96 patients were analyzed. The median follow-up period was 61 months. The 3-year relapse-free survival, overall survival (OS), and locoregional relapse-free survival (LRFS) rates were 76%, 90%, and 88%, respectively. In multivariate analysis, the histological finding of either adenocarcinoma or adenosquamous carcinoma was a significant risk factor for both OS and LRFS. The percentage of patients with grade ≥ 3 acute hematologic toxicity, acute lower gastrointestinal toxicity (GIT), and late lower GIT were 45%, 19%, and 17%, respectively. CONCLUSIONS: The outcomes of concurrent chemoradiotherapy (CCRT) using weekly 40-mg/m2 cisplatin are similar to those in the previous studies that used several chemotherapy regimens. However, postoperative CCRT using 3DRT had a high level of late GIT.

Preoperative diffusion-weighted magnetic resonance imaging and intraoperative frozen sections for predicting the tumor grade in endometrioid endometrial cancer.

OBJECTIVE: The histological tumor grade is a strong predictor of nodal metastasis in endometrial cancer; as such, an accurate pre- or intraoperative diagnosis is important for performing lymphadenectomy. METHODS: Ninety-one patients with endometrioid endometrial cancer were imaged on DW-MRI with the apparent diffusion coefficient (ADC) calculated and a frozen section (FS) diagnosis made before and at hysterectomy. The diagnostic accuracy for predicting the tumor grade for diffusion weighted magnetic resonance inaging (DW-MRI) and the FS diagnosis compared to the ultimate histologic status was analyzed. RESULTS: Among 91 patients with endometrioid endometrial cancer, high-grade (endometrioid G3) tumors had lower ADC values than low-grade (endometrioid G1/2) tumors. The cut-off of the mean ADCmean values for predicting high-grade tumors resulted in 743×10-6 mm2/sec according to the receiver operating characteristic curve. The true positive rates of ADC values and FSs for the prediction of high-grade tumors did not differ to a statistically significant extent (73.3% vs. 66.7%, p=0.7), however, the true negative rate of ADC values for the prediction of low-grade tumors was significantly lower than that of the FSs (64.5% vs. 98.7%, p=0.01). The kappa statistics of ADC values and FSs were 0.23 and 0.73, respectively. Of note, all five patients with high-grade tumors for whom intraoperative FSs indicated low-grade tumors were predicted to have high-grade tumors on preoperative DW-MRI. CONCLUSION: A FS diagnosis is more suitable for predicting high-grade tumors than DW-MRI; however, physicians should pay close attention to tumors with low ADC values on preoperative DW-MRI.

Neoadjuvant intra-arterial chemotherapy using an original four-lumen double-balloon catheter for locally advanced uterine cervical cancer.

OBJECTIVE: We report a balloon-occluded arterial infusion therapy with an original four-lumen double-balloon catheter (4L-DB) which allows for the efficient injection of an anticancer agent at a high concentration to the target spot for patients with locally advanced uterine cervical cancer. METHODS: One hundred and forty-three patients with locally advanced cervical cancer treated with neoadjuvant intra-arterial chemotherapy (NAIAC) or a primary radical hysterectomy (PRH) were retrospectively assessed. The patients in the NAIAC group received irinotecan 70 mg/m2 intravenously on day 1 and 8 and cisplatin 70 mg/m2 intra-arterially using the 4L-DB on day 2 of a 21-day course, and two courses were performed in principle. The radical hysterectomy was performed within 6 weeks after NAIAC. RESULTS: Ninety-four patients were treated with NAIAC, and 49 patients undertook a PRH. The response rate of NAIAC on MRI was 92.6%. Fourteen patients (14.6%) had no evidence of cancer cells on pathologic diagnoses. The NAIAC group had a longer disease-free survival than the PRH group (p=0.02); however, the overall survival was not significantly different. The relative risk (RR) for recurrence was higher in patients with lymph node metastasis (RR, 4.31; 95% CI, 2.23-8.43) and lower in those who underwent NAIAC (RR, 0.30; 95% CI, 0.14-0.68). CONCLUSION: Our results with NAIAC using the 4L-DB catheter in locally advanced cervical cancer indicates beneficial effects on primary lesions and improves disease-free survival.

The detection of sentinel lymph nodes in laparoscopic surgery can eliminate systemic lymphadenectomy for patients with early stage endometrial cancer.

BACKGROUND: The examination of a sentinel lymph node (SLN), where lymph node metastasis first occurs, may be advocated as an alternative staging technique. The aim of this study was to evaluate the feasibility and detection rates of an SLN biopsy in patients with endometrial cancer. STUDY DESIGN: Two hundred and eleven patients with endometrial cancer underwent an SLN biopsy at hysterectomy using three kinds of tracers including 99m-technetium-labeled tin colloid (99mTc), indigo carmine and indocyanine green. Factors related to the side-specific detection rate, sensitivity and false negative rate were analyzed. RESULTS: The detection rates of the SLN biopsy using 99mTc, indigo carmine and indocyanine green were 77.9, 17.0 and 73.4%, respectively. The detection rate was lower in elderly patients (≥60 years) (67.9 vs 89.2%, p < 0.01), patients with >50% myometrial invasion (68.3 vs 85.2%, p < 0.01), patients with high-grade tumors (69.5 vs 84.9%, p < 0.01) and patients who underwent laparotomy (71.2 vs 84.9%, p < 0.01). There were no significant differences in body mass index. The sensitivity was not significantly different in any factor. However, the false negative rate was higher in patients with > 50% myometrial invasion (11.5 vs 1.2%, p < 0.01), high-grade tumors (13.3 vs 0.8%, p < 0.01) and who underwent laparotomy (12.2 vs 0.4%, p < 0.01). CONCLUSION: Patients who underwent laparoscopy with < 50% myometrial invasion and low-grade tumors not only have higher detection rates, but also have lower false negative rates. These patients may avoid systemic lymphadenectomy according to the status of the SLN biopsy.

The efficacy of the cyclin-dependent kinase 4/6 inhibitor in endometrial cancer.

BACKGROUND: PD-0332991, the selective cyclin-dependent kinase 4/6 inhibitor palbociclib, causes cell cycle arrest by inhibiting phosphorylation of retinoblastoma (Rb) protein. The aim of this study was to evaluate the therapeutic potential of PD-0332991 in endometrial cancer. METHODS AND FINDINGS: Four human endometrial cancer cell lines, ECC, HEC1A, HEC108 and TEN, were treated with PD-0332991 and their function was evaluated. In vivo, the therapeutic efficacy was evaluated in a model of subcutaneous endometrial cancer. An immunohistochemical analysis was performed in 337 endometrial cancer specimens. A proliferation assay revealed that 2 of the 4 cell lines that expressed Rb were sensitive to PD-0332991 with an IC50 of 0.65 µM (HEC1A) and 0.58 µM (HEC108), respectively. Both cell lines had G0/G1 cell cycle arrest after treatment with PD-0332991 according to flow cytometry. In vivo, PD-0332991 had antitumoral efficacy with a reduction in the activity of Ki67 and phosphorylation of Rb. Immunohistochemical analyses revealed that the positive rate of Rb was 67.7%, however, there was no significant relationship between the expression levels of Rb and the tumor grade. CONCLUSIONS: PD-0332991 had therapeutic potential against endometrial cancer cell lines expressing Rb protein. Our immunohistochemical analysis revealed that approximately 70% of patients with endometrial cancer might have therapeutic indications for PD-0332991. Of note, the tumor grade had no impact on the indications for treatment.